Publication Information

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'https://openalex.org/W2049595664'], 'abstract_inverted_index': {'Membrane': [0, 198, 396], 'type': [1, 199, 397, 816, 1519, 2415, 2438, 2556, 2730, 3536, 3703, 3785, 4076, 4090, 4786], '1-matrix': [2, 200, 398], 'metalloproteinase': [3, 201, 399], '(MT1-MMP)': [4, 202], 'is': [5, 21, 36, 77, 165, 178, 203, 219, 234, 275, 363, 376, 435, 448, 525, 634, 646, 756, 773, 869, 1005, 1020, 1044, 1186, 1193, 1745, 1755, 1762, 1820, 1826, 1838, 1941, 2008, 2058, 2077, 2116, 2279, 2361, 2485, 2505, 2534, 2637, 2645, 2666, 2823, 2842, 2846, 3108, 3393, 3461, 3474, 3496, 3528, 3542, 3564, 4242, 4271, 4283, 4330, 4407, 4427, 4535, 4543, 4587, 4611, 4667, 4671, 4746, 4760, 4768, 4790, 4825, 4913, 4916, 4923, 5135], 'a': [6, 25, 109, 125, 191, 204, 223, 307, 323, 389, 411, 436, 635, 647, 651, 666, 694, 697, 700, 704, 796, 874, 1023, 1202, 1238, 1364, 1693, 1796, 1892, 2028, 2161, 2373, 2582, 2818, 2852, 2873, 2983, 2993, 3053, 3057, 3139, 3346, 3484, 3553, 3770, 3987, 4019, 4181, 4313, 4456, 4477, 4507, 4654, 4736, 4924, 5140, 5150, 5155], 'zinc-dependent,': [7, 205], 'membrane-associated': [8, 206, 762], 'endoproteinase': [9, 207], 'of': [10, 23, 28, 34, 44, 51, 108, 124, 133, 143, 160, 169, 208, 221, 226, 232, 242, 249, 306, 322, 331, 341, 358, 367, 427, 432, 438, 442, 453, 532, 603, 629, 659, 670, 673, 706, 712, 716, 761, 771, 781, 806, 814, 872, 883, 1001, 1013, 1018, 1022, 1027, 1041, 1057, 1069, 1076, 1176, 1196, 1233, 1248, 1416, 1439, 1482, 1546, 1592, 1604, 1633, 1655, 1668, 1696, 1704, 1733, 1751, 1791, 1845, 1860, 1870, 1885, 1903, 1950, 1954, 1969, 1990, 1992, 2013, 2031, 2039, 2053, 2068, 2080, 2119, 2175, 2183, 2187, 2211, 2281, 2293, 2317, 2329, 2358, 2395, 2401, 2413, 2421, 2436, 2444, 2477, 2490, 2501, 2537, 2552, 2589, 2596, 2610, 2614, 2628, 2633, 2641, 2658, 2664, 2694, 2706, 2732, 2745, 2750, 2761, 2837, 2870, 2890, 2905, 2946, 2952, 2969, 2975, 2990, 2995, 3006, 3039, 3063, 3066, 3138, 3145, 3151, 3157, 3162, 3173, 3179, 3189, 3226, 3233, 3243, 3259, 3262, 3285, 3290, 3303, 3307, 3348, 3363, 3420, 3437, 3470, 3478, 3500, 3508, 3533, 3552, 3574, 3605, 3615, 3630, 3652, 3661, 3689, 3706, 3721, 3731, 3774, 3804, 3810, 3842, 3851, 3854, 3862, 3868, 3882, 3897, 3923, 3931, 3935, 3961, 3966, 3991, 4011, 4029, 4069, 4096, 4101, 4128, 4191, 4199, 4246, 4260, 4300, 4305, 4339, 4344, 4377, 4400, 4405, 4414, 4435, 4459, 4483, 4487, 4517, 4558, 4562, 4579, 4609, 4618, 4661, 4705, 4719, 4731, 4742, 4778, 4852, 4860, 4865, 4872, 4881, 4935, 5080, 5091, 5094, 5116, 5142, 5173, 5183], 'the': [11, 41, 70, 83, 106, 134, 141, 157, 161, 209, 239, 268, 281, 304, 332, 339, 355, 359, 439, 443, 451, 519, 526, 630, 643, 656, 660, 674, 690, 713, 757, 803, 807, 822, 867, 904, 1002, 1010, 1014, 1028, 1036, 1064, 1073, 1081, 1170, 1173, 1217, 1280, 1458, 1475, 1530, 1539, 1590, 1666, 1669, 1701, 1725, 1746, 1749, 1756, 1763, 1821, 1827, 1839, 1871, 1883, 1901, 1946, 1988, 2011, 2034, 2037, 2051, 2065, 2069, 2117, 2131, 2171, 2179, 2197, 2207, 2212, 2282, 2286, 2288, 2291, 2294, 2301, 2315, 2318, 2326, 2335, 2339, 2342, 2345, 2350, 2381, 2391, 2398, 2402, 2408, 2418, 2433, 2441, 2475, 2531, 2590, 2593, 2608, 2611, 2615, 2622, 2656, 2695, 2703, 2707, 2746, 2764, 2826, 2829, 2833, 2847, 2859, 2879, 2891, 2903, 2925, 2929, 2973, 2986, 2996, 3003, 3061, 3064, 3105, 3119, 3135, 3149, 3152, 3155, 3159, 3174, 3177, 3186, 3199, 3203, 3224, 3244, 3263, 3282, 3387, 3394, 3398, 3410, 3418, 3421, 3425, 3447, 3450, 3457, 3465, 3475, 3479, 3506, 3509, 3524, 3534, 3544, 3561, 3565, 3586, 3603, 3613, 3622, 3627, 3631, 3642, 3648, 3687, 3690, 3701, 3711, 3719, 3729, 3787, 3801, 3811, 3843, 3860, 3863, 3869, 3898, 3921, 3924, 3929, 3992, 4004, 4008, 4015, 4027, 4030, 4049, 4062, 4067, 4102, 4108, 4125, 4129, 4140, 4188, 4196, 4200, 4243, 4256, 4272, 4291, 4298, 4306, 4317, 4320, 4340, 4342, 4345, 4351, 4356, 4367, 4374, 4398, 4415, 4430, 4436, 4460, 4493, 4524, 4537, 4563, 4570, 4580, 4585, 4600, 4607, 4615, 4619, 4623, 4701, 4706, 4729, 4755, 4758, 4775, 4779, 4799, 4805, 4815, 4829, 4849, 4858, 4873, 4879, 4884, 4890, 4893, 4896, 4902, 4918, 4936, 5078, 5092, 5095, 5099, 5113, 5124, 5130, 5136, 5161, 5171, 5181], 'metzincin': [12, 210, 444, 675], 'family.': [13, 211, 445], 'The': [14, 31, 72, 118, 131, 212, 229, 270, 316, 329, 446, 662, 769, 809, 880, 998, 1016, 1032, 1276, 1542, 1631, 1789, 1808, 2001, 2110, 2446, 2617, 2630, 2661, 2668, 2692, 3358, 3491, 3538, 3663, 3723, 3840, 3866, 3894, 3941, 4402, 4411, 4444, 4626, 4744, 4748, 4766, 4842], 'enzyme': [15, 213, 447, 637, 672, 1376, 1705, 1758, 1786, 1848, 4531], 'regulates': [16, 214, 655], 'extracellular': [17, 215, 454], 'matrix': [18, 216, 408, 421, 455], 'remodeling': [19, 217, 459], 'and': [20, 149, 184, 218, 347, 382, 413, 457, 543, 610, 703, 767, 892, 900, 1008, 1043, 1060, 1066, 1253, 1264, 1380, 1435, 1480, 1492, 1520, 1544, 1554, 1610, 1760, 1836, 1849, 1880, 1938, 1952, 1971, 2015, 2017, 2025, 2143, 2152, 2178, 2189, 2277, 2290, 2348, 2397, 2451, 2510, 2519, 2521, 2548, 2592, 2601, 2624, 2635, 2639, 2643, 2690, 2713, 2832, 2865, 2881, 2917, 2939, 2979, 3002, 3009, 3126, 3181, 3216, 3238, 3277, 3287, 3297, 3384, 3520, 3626, 3672, 3677, 3682, 3692, 3834, 3856, 3888, 3912, 3957, 4048, 4145, 4151, 4158, 4203, 4205, 4249, 4285, 4365, 4453, 4529, 4597, 4640, 4644, 4647, 4652, 4683, 4689, 4721, 4817, 4854, 4875, 4895, 4941, 5106, 5123, 5185], 'capable': [22, 220, 871, 1195, 2079, 2536, 2749, 3302], 'cleaving': [24, 222], 'wide': [26, 224], 'variety': [27, 225], 'transmembrane': [29, 227, 701], 'proteins.': [30, 228], 'enzymatic': [32, 230, 4197], 'activity': [33, 68, 231, 266, 658, 770, 1545, 1600, 2055, 3720, 4608, 5114], 'MT1-MMP': [35, 104, 233, 302, 524, 633, 717, 793, 819, 1281, 1375, 1785, 1889, 1964, 1970, 2018, 2042, 2057, 2553, 2723, 2762, 2981, 3133, 3230, 3253, 3428, 3513, 3610, 3734, 3823, 3962, 4034, 4116, 4446, 4475, 4530, 4574, 4734, 4794, 4855, 5189], 'regulated': [37, 235, 774], 'by': [38, 105, 140, 236, 303, 338, 721, 775, 794, 1206, 1424, 1450, 1484, 1556, 1637, 1778, 1857, 2022, 2148, 2192, 2201, 2276, 2431, 2737, 2872, 2954, 3502, 3708, 4239, 4519, 4565, 4700, 4771, 4838], 'endogenous': [39, 237, 777, 4189], 'inhibitors,': [40, 238, 778], 'tissue': [42, 240, 430, 458, 779], 'inhibitor': [43, 102, 241, 300, 431, 780, 1765, 3251, 3557, 4016], 'metalloproteinases': [45, 243, 782], '(TIMP).': [46, 244, 783], 'To': [47, 245, 753, 4036], 'date,': [48, 246, 754], 'four': [49, 247, 786, 3809], 'variants': [50, 248], 'mammalian': [52, 250, 787], 'TIMP': [53, 251, 791, 884, 1077, 1548, 1850, 1863, 1872, 2176, 2597, 2849, 2897, 3480, 4187, 4882, 4939, 5118, 5144], 'have': [54, 252, 1462, 2019, 2463, 2851, 2901, 3581, 4000, 4288], 'been': [55, 253, 1179, 1286, 1463, 1472, 1891, 2020, 4931, 5146], 'identified.': [56, 254], 'Whereas': [57, 255], 'TIMP-2-4': [58, 256, 817, 859, 1955, 2672, 3163, 3495], 'are': [59, 257, 693, 785, 820, 860, 906, 1050, 1874, 2144, 2304, 2456, 2604, 2673, 2697, 2862, 3128, 3633, 3670, 3845, 4026, 4051, 4186, 4236, 4363, 4451, 4630, 4691, 4711, 4889, 5110], 'potent': [60, 258, 3667, 3793], 'inhibitors': [61, 259, 862, 3131, 4190], 'against': [62, 69, 90, 103, 260, 267, 288, 301, 863, 1224, 1558, 1601, 1617, 2041, 2056, 2417, 3132, 3229, 3427, 3512, 3594, 3733, 4071, 4162, 4280, 4573, 4733, 4820, 5088, 5154], 'MT1-MMP,': [63, 261, 405, 864, 2085, 3118, 4072], 'TIMP-1': [64, 88, 95, 262, 286, 293, 899, 1192, 1222, 1441, 1609, 1867, 1886, 1951, 1972, 1993, 2014, 2040, 2054, 2076, 2125, 2330, 2634, 2665, 2838, 2841, 2976, 3165, 3200, 3227, 3473, 3592, 4012, 4070, 4077, 4091, 4150, 4278, 4301, 4505, 4528, 4789, 4853], 'displays': [65, 263, 665], 'negligible': [66, 264], 'inhibitory': [67, 122, 158, 265, 320, 356, 1243, 1599, 3549, 3569], 'enzyme.': [71, 269, 661, 808, 2132], 'rationale': [73, 271, 3156], 'for': [74, 195, 272, 393, 1181, 1268, 1279, 1677, 1866, 1896, 1959, 2027, 2094, 2112, 2937, 3055, 3110, 4726, 4754, 5180, 5188], 'such': [75, 273, 539, 4247], 'selectivity': [76, 274, 1905, 2612, 4906], 'hitherto': [78, 276, 1184, 2044], 'unknown.': [79, 277], 'Here': [80, 278, 1199, 2908], 'we': [81, 279, 1200, 1236, 2048, 2073, 2114, 2164, 2324, 2429, 2650, 2909, 3192, 3580, 3617, 3807, 3999, 4040, 4491, 4540, 4697, 4845, 4899], 'identify': [82, 280], 'surface': [84, 282, 1218, 2066, 4399], 'epitopes': [85, 283, 1219, 1230, 2369, 2387, 3814, 4006, 4709], 'that': [86, 94, 175, 284, 292, 373, 649, 654, 903, 1072, 1172, 1220, 1241, 1467, 1532, 1956, 1984, 2009, 2050, 2075, 2089, 2123, 2196, 2640, 3048, 3104, 3214, 3299, 3391, 3417, 3482, 3532, 3543, 3590, 3660, 4013, 4061, 4107, 4269, 4276, 4349, 4425, 4515, 4542, 4584, 4606, 4703, 4804, 4828, 4856, 4901, 4917, 4928], 'render': [87, 285, 1221], 'inactive': [89, 287, 1223, 3593, 4279, 5143], 'MT1-MMP.': [91, 289, 879, 1198, 1225, 2000, 2184, 2445, 2964, 3190, 3210, 3595, 4024, 4281, 4821], 'We': [92, 290, 1213, 3279, 5109, 5159, 5176], 'show': [93, 291, 4900], 'can': [96, 294, 4250], 'be': [97, 137, 295, 335, 765, 2092, 2140, 2308, 2372, 3247, 3585, 3598, 3949, 4388, 4476, 4599, 4752, 4835, 5127], 'transformed': [98, 296, 5148], 'into': [99, 297, 908, 1433, 1719, 2206, 2331, 2363, 2621, 4045, 4724, 5149], 'an': [100, 298, 671, 1731, 2086, 2203, 3142, 3435, 3816], 'active': [101, 299, 1547, 1616, 3782, 5087, 5152], 'mutation': [107, 305, 1470], 'single': [110, 308, 2374], 'residue,': [111, 309], 'namely': [112, 310, 789, 2334, 2688, 3275, 4637], 'threonine': [113, 176, 311, 374, 2638, 3485, 3501], '98': [114, 177, 312, 375], 'to': [115, 146, 152, 313, 344, 350, 764, 888, 1190, 1465, 1661, 1692, 1699, 1729, 1784, 1887, 1962, 1979, 1994, 2061, 2091, 2156, 2166, 2170, 2307, 2479, 2508, 2850, 2912, 2920, 3112, 3168, 3352, 3369, 3408, 3434, 3452, 3572, 3584, 3600, 3620, 3818, 3880, 3948, 4302, 4311, 4316, 4361, 4387, 4449, 4509, 4545, 4635, 4735, 4740, 4814, 4904], 'leucine': [116, 314, 3392, 3453, 3503, 4289, 4296, 4510, 4520, 4596], '(T98L).': [117, 315], 'resultant': [119, 317, 2403, 3510], 'mutant': [120, 135, 163, 318, 333, 361, 1240, 1522, 1613, 2654, 3405, 3445, 3454, 3511, 3546, 3567, 3654, 3788, 3872, 3899, 4131], 'displayed': [121, 319, 4078], 'characteristics': [123, 321, 4617], 'typical': [126, 324, 669, 1021], 'slow,': [127, 325, 3554], 'tight': [128, 326, 875, 1721, 1996, 2095, 2539, 2752, 2947, 3114, 3249, 3555, 4020], 'binding': [129, 183, 327, 381, 810, 876, 1722, 2434, 2447, 2540, 2720, 2948, 2961, 3115, 3250, 3556, 4021, 4299, 4571], 'inhibitor.': [130, 328, 2616], 'potency': [132, 330, 1244, 1667], 'could': [136, 334, 1957, 1985, 2370, 3183, 3246, 4470, 4750, 4834], 'further': [138, 336], 'enhanced': [139, 337, 3505, 4728], 'introduction': [142, 340], 'valine': [144, 153, 342, 351, 2913, 3671, 4566], '4': [145, 343], 'alanine': [147, 345, 2677, 2866, 2918, 2955], '(V4A)': [148, 346], 'proline': [150, 348, 2853], '6': [151, 349], '(P6V)': [154, 352], 'mutations.': [155, 353], 'Indeed,': [156, 354, 3498, 3523], 'profile': [159, 357, 2613], 'triple': [162, 360, 3832, 3871], '(V4A/P6V/T98L)': [164, 362], 'indistinguishable': [166, 364, 1245, 3658], 'from': [167, 365, 886, 1246, 1257, 1272, 1659, 2126, 3205, 3281, 3367, 3431, 3456, 3659, 4017, 4373], 'those': [168, 366, 1232, 1247, 1953, 3374, 3573, 3881, 4631, 4741], 'other': [170, 368, 537, 627, 1037, 1234, 1249, 2532, 3388, 3606, 3712, 4286, 5103], 'TIMPs.': [171, 369, 1250], 'Our': [172, 187, 370, 385, 3211, 4512], 'findings': [173, 188, 371, 386, 3120, 4773, 4830, 5125, 5162], 'suggest': [174, 372], 'critical': [179, 377], 'in': [180, 378, 450, 535, 725, 821, 1054, 1209, 1215, 1288, 1345, 1384, 1419, 1489, 1538, 1549, 1562, 1748, 1877, 1900, 1974, 2005, 2084, 2136, 2160, 2458, 2474, 2493, 2581, 2607, 2671, 2699, 2719, 2817, 2928, 2960, 3195, 3222, 3252, 3310, 3376, 3446, 3494, 3635, 3769, 3800, 3815, 3847, 3986, 4002, 4053, 4180, 4213, 4234, 4389, 4463, 4474, 4480, 4496, 4591, 4633, 4658, 4793, 4831, 4848, 4908, 4933, 5129, 5138, 5163], 'initiating': [181, 379, 2127, 3206], 'MMP': [182, 380, 763, 4592, 5157], 'complex': [185, 383, 801, 877, 1998, 2098, 2753, 3041, 3116, 4022, 4323, 4417, 4503], 'stabilization.': [186, 384], 'also': [189, 387, 601, 1977, 4194, 4552], 'provide': [190, 388, 4312], 'potential': [192, 390], 'mechanistic': [193, 391], 'explanation': [194, 392, 1188], 'MMP-TIMP': [196, 394], 'selectivity.': [197, 395, 5175], '(MT1-MMP,': [400], '1The': [401], 'abbreviations': [402], 'used': [403], 'are:': [404], 'membrane': [406], 'type-1': [407], 'metalloproteinase;': [409, 414], 'ADAM,': [410], 'disintegrin': [412], 'ADAM-TS,': [415], 'ADAM': [416, 4201, 5105], 'with': [417, 607, 626, 638, 802, 818, 878, 1231, 1363, 1371, 1527, 1529, 1622, 1652, 1724, 1737, 1999, 2130, 2390, 2440, 2542, 2554, 2722, 2755, 2763, 2963, 3117, 3185, 3209, 3744, 3963, 4023, 4208, 4392, 4504, 4677, 4763, 4784, 4883, 4887, 5077, 5120], 'thrombospondin-like': [418, 4209], 'repeats;': [419], 'MMPs,': [420, 4192, 4233, 5104], 'metalloproteinases;': [422], 'N-TIMP,': [423], 'N-terminal': [424, 999, 1067, 1082, 1436, 2172, 2585, 4009, 4084, 4141], 'domain': [425, 645, 664, 692, 715, 805, 1000, 1056, 1083, 1437, 2173, 2181, 2443, 4010, 4032, 4064, 4110, 4807], 'form': [426, 1995, 2182], 'TIMP;': [428], 'TIMP,': [429, 1235], 'metalloproteinases.': [433], 'MMP-14)': [434], 'member': [437, 3477], 'zinc-dependent': [440], 'endopeptidases': [441], 'involved': [449, 4590], 'degradation': [452], 'components': [456], '(1Galvez': [460], 'B.G.': [461], 'Matias-Roman': [462], 'S.': [463, 1091, 5047], 'Albar': [464], 'J.P.': [465], 'Sanchez-Madrid': [466], 'F.': [467, 937, 1131, 2241, 3313, 5010], 'Arroyo': [468], 'A.G.': [469], 'J.': [470, 552, 584, 744, 842, 926, 987, 1329, 1398, 1912, 2231, 3028, 3086, 4221, 4965, 5056], 'Biol.': [471, 509, 585, 683, 843, 989, 1399, 3087, 5057], 'Chem.': [472, 586, 844, 1400, 3088, 4967, 5058], '2001;': [473, 684, 1161, 1304, 3089], '276:': [474, 3090], '37491-37500Abstract': [475], 'Full': [476, 478, 590, 592, 848, 850, 1404, 1406, 3092, 3094, 5062, 5064], 'Text': [477, 479, 591, 593, 849, 851, 1405, 1407, 3093, 3095, 5063, 5065], 'PDF': [480, 594, 852, 1408, 3096, 5066], 'PubMed': [481, 496, 513, 563, 595, 620, 748, 853, 931, 964, 993, 1102, 1123, 1144, 1164, 1307, 1333, 1409, 1512, 1581, 1918, 2235, 2268, 3032, 3097, 3340, 4227, 4971, 5000, 5027, 5041, 5067], 'Scopus': [482, 497, 514, 564, 596, 621, 749, 854, 932, 965, 994, 1103, 1124, 1145, 1165, 1308, 1334, 1410, 1513, 1582, 1919, 1933, 2236, 2269, 3033, 3098, 3341, 4228, 4955, 4972, 5001, 5028, 5042, 5068], '(206)': [483], 'Google': [484, 499, 516, 566, 598, 623, 687, 751, 856, 934, 967, 996, 1105, 1126, 1147, 1167, 1310, 1336, 1412, 1515, 1584, 1921, 1935, 2238, 2271, 3035, 3100, 3343, 4230, 4957, 4974, 5003, 5030, 5044, 5070], 'Scholar,': [485, 500, 567, 935, 968, 1106, 1127, 1148, 1311, 1922, 2239, 4958, 4975, 5004, 5031, 5045], '2Egeblad': [486], 'M.': [487, 558, 614, 941, 1116, 1135, 2245, 3075, 3079, 3317], 'Werb': [488], 'Z.': [489], 'Nat.': [490, 505], 'Rev.': [491, 506], 'Cancer.': [492], '2002;': [493, 510, 1330, 1509, 1578, 1915, 1930, 4224, 4952], '2:': [494], '161-174Crossref': [495], '(5134)': [498], '3Brinckerhoff': [501], 'C.E.': [502], 'Matrisian': [503], 'L.': [504, 4985, 5051], 'Mol.': [507, 682, 988], 'Cell.': [508], '3:': [511], '207-214Crossref': [512], '(969)': [515], 'Scholar).': [517, 624, 688, 752, 857, 997, 1168, 1337, 1413, 1516, 1936, 2109, 2272, 3036, 3344, 4231, 5071], 'Among': [518, 2702], 'six': [520], 'membrane-type': [521], 'MMPs': [522, 538, 772, 2200, 4888], 'identified,': [523], 'most': [527, 2002, 3539, 3666, 4914], 'studied': [528], 'not': [529, 870, 1194, 2059, 2078, 2145, 2535, 3122, 3167, 3791, 3946, 4385, 4522, 4536, 4588, 4712, 4751], 'only': [530, 758, 2652, 2848, 3395, 3403, 3423, 3476, 4185, 4538, 4868], 'because': [531, 602, 4073], 'its': [533, 604, 1611, 1960, 2991, 3000, 4083, 4481, 4674], 'role': [534], 'activating': [536], 'as': [540, 1189, 1382, 1494, 1526, 1560, 2844, 3052, 3371, 3373, 3646, 3792, 3794, 4716], 'pro-MMP-2': [541], '(pro-gelatinase-A)': [542], 'pro-MMP-13': [544], '(4Sato': [545], 'H.': [546, 571, 579, 740, 951, 957, 1089, 1389, 1924, 2227, 2255, 2261, 3024, 3327, 3333, 4946, 4977, 5014, 5016, 5035, 5053], 'Takino': [547], 'T.': [548], 'Okada': [549], 'Y.': [550, 976, 4994, 5021, 5049], 'Cao': [551], 'Shinagawa': [553], 'A.': [554, 738, 835, 837, 943, 970, 1110, 1325, 2225, 2247, 3022, 3319], 'Yamamoto': [555], 'E.': [556, 972, 1490], 'Seiki': [557], 'Nature.': [559, 960, 2264, 3336], '1994;': [560, 928, 1141], '370:': [561], '61-65Crossref': [562], '(2373)': [565], '5Knäuper': [568], 'V.': [569, 833, 1152, 1295, 1315, 1321, 1502, 1571, 3081, 4055, 4981, 5186], 'Will': [570], 'Lopez-Otin': [572, 838], 'C.': [573, 728, 839, 980, 2215, 3012, 5008], 'Smith': [574, 1394], 'B.': [575, 1395], 'Atkinson': [576, 1390], 'S.J.': [577, 1391], 'Stanton': [578], 'Hembry': [580], 'R.M.': [581], 'Murphy': [582, 840, 919, 1138, 1155, 1298, 1326, 1396, 1505, 1574, 1910, 3084, 4219], 'G.': [583, 841, 916, 920, 986, 1108, 1139, 1156, 1299, 1327, 1397, 1506, 1575, 1911, 3077, 3085, 4220, 5178], '1996;': [587, 1099, 1401], '271:': [588, 1402], '17124-17131Abstract': [589], '(620)': [597], 'Scholar),': [599], 'but': [600], 'compelling': [605], 'link': [606], 'cell': [608], 'invasion': [609], 'tumor': [611], 'malignancy': [612], '(6Seiki': [613], 'Cancer': [615], 'Lett.': [616, 1098], '2003;': [617, 5038, 5059], '194:': [618], '1-11Crossref': [619, 4999], '(363)': [622], 'As': [625, 4485, 4547, 5072], 'members': [628, 1869], 'matrixin': [631], 'family,': [632], 'multidomain': [636], 'clear': [639], 'structural': [640, 2153], 'compartmentation.': [641], 'Preceding': [642], 'catalytic': [644, 657, 663, 691, 714, 804, 2180, 2208, 2442, 2626, 4352], 'propeptide': [648], 'contains': [650, 2982], 'cysteine': [652], 'switch': [653], 'tertiary': [667, 1881], 'fold': [668], 'family': [676, 1873, 3481], '(7Bode': [677], 'W.': [678, 730, 959, 982, 1085, 2217, 2263, 3014, 3335, 4983, 4987, 5006], 'Maskos': [679, 741, 938, 977, 1316, 1499, 1568, 2228, 2242, 3025, 3314, 4988, 5017], 'K.': [680, 742, 939, 947, 953, 978, 984, 1087, 1096, 1317, 1500, 1569, 1926, 2229, 2243, 2251, 2257, 3026, 3315, 3323, 3329, 4948, 4989, 4991, 5018, 5055], 'Methods': [681, 2104], '151:': [685], '45-77PubMed': [686], 'Succeeding': [689], 'short': [695], 'hinge,': [696], 'hemopexin': [698], 'domain,': [699, 702, 1034], 'cytotail': [705], '2.5': [707], 'kDa.': [708, 890], 'A': [709], 'crystal': [710, 2892, 3283, 4412], 'structure': [711, 1175, 3038, 4413, 4582], 'was': [718, 1377, 1536, 1635, 1650, 1672, 1690, 1793, 1806, 1811, 2426, 2748, 2943, 3166, 3301, 3406, 3449, 3779, 3789, 3877, 4136, 4551, 4808], 'first': [719, 1011, 1841, 2765, 2834, 3566, 4057, 5137], 'reported': [720, 1561], 'Fernandez-Catalan': [722, 979, 5007], 'et': [723, 3070], 'al.': [724, 3071], '1998': [726], '(8Fernandez-Catalan': [727, 2214, 3011], 'Bode': [729, 958, 981, 2216, 2262, 3013, 3334, 4986], 'Huber': [731, 944, 2218, 2248, 3015, 3320], 'R.': [732, 945, 2219, 2249, 3016, 3321, 5033], 'Turk': [733, 2220, 3017], 'D.': [734, 1319, 2221, 3018], 'Calvete': [735, 2222, 3019], 'J.J.': [736, 2223, 3020], 'Lichte': [737, 2224, 3021], 'Tschesche': [739, 2226, 3023, 5015], 'EMBO': [743, 2230, 3027], '1998;': [745, 990, 2232, 3029], '17:': [746, 2233, 3030], '5238-5248Crossref': [747, 2234, 3031], '(311)': [750, 2237, 3034], 'this': [755, 1211, 1420, 1713, 2158, 2322, 2686, 2855, 2906, 3049, 3273, 3356, 3487, 3805, 4038, 4471, 4695, 4832, 5164], 'known': [759], 'variant': [760, 3396, 5141], 'crystallized': [766], 'published.': [768], 'their': [776, 1605, 1619, 2469, 3820, 4861, 4876], 'There': [784, 1049], 'TIMPs,': [788], 'TIMP-1-4.': [790], 'inhibit': [792, 1888, 1963, 2199], 'forming': [795, 873], 'tight,': [797], 'non-covalent': [798], '1:1': [799], 'stoichiometric': [800], 'constants': [811], '(K': [812, 1645, 2449, 2495, 2724, 2739, 2933, 3231, 3429, 3514, 3674, 3873, 3884, 3890, 3933, 4086, 4118], 'iapp)': [813, 2450], 'wild': [815, 1518, 2437, 2555, 2729, 3535, 3702, 3784, 4075, 4089, 4785], 'low': [823], 'picomolar': [824], 'range': [825, 2476], '(9English': [826], 'W.R.': [827], 'Puente': [828], 'X.S.': [829], 'Freije': [830], 'J.M.': [831], 'Knäuper': [832, 1151, 1294, 1320, 1501, 1570, 3080, 5187], 'Amour': [834, 1324], 'Merryweather': [836], '2000;': [845], '275:': [846], '14046-14055Abstract': [847], '(183)': [855], 'Although': [858, 3068], 'superb': [861], 'TIMP-1,': [865, 4047], 'on': [866, 898, 1035, 1063, 1457, 1586, 1665, 1772, 1774, 1853, 1862, 2321, 2380, 2513, 2530, 2562, 2896, 3176, 3609, 3710, 3718, 3822, 3901, 3915, 3972, 3995, 4007, 4033, 4115, 4167, 4397, 4555, 4614, 4774, 4798, 4938, 5170], 'contrary,': [868], 'molecular': [881, 4258, 4850], 'masses': [882], 'vary': [885], '21': [887], '28': [889], 'Crystallography': [891], 'protein': [893, 1639, 1897, 2023, 4251], 'NMR': [894, 2024, 2894], 'studies': [895, 4864], 'carried': [896, 2427], 'out': [897, 3170, 3197, 3602], '-2': [901, 2016], 'revealed': [902, 4106], 'molecules': [905], 'folded': [907], 'two': [909, 2070, 2681, 3267, 3665, 4357, 4445], 'very': [910, 2283], 'discrete': [911], 'domains': [912], '(10Williamson': [913], 'R.A.': [914, 1114, 3073], 'Martorell': [915], 'Carr': [917, 3082], 'M.D.': [918, 3083], 'Docherty': [921, 1117, 1136], 'A.J.': [922], 'Freedman': [923], 'R.B.': [924], 'Feeney': [925], 'Biochemistry.': [927, 1119, 1140], '33:': [929, 1142], '11745-11759Crossref': [930], '(95)': [933], '11Gomis-Rüth': [936, 2240], 'Betz': [940, 2244, 3316], 'Bergner': [942, 2246, 3318], 'Suzuki': [946, 1086, 2250, 3322], 'Yoshida': [948, 2252, 3324], 'N.': [949, 2253, 3325, 4993, 5020], 'Nagase': [950, 1088, 2254, 3326, 5013, 5034, 5052], 'Brew': [952, 1095, 1925, 2256, 3328, 4947, 4990, 5054], 'Bourenkov': [954, 2258, 3330], 'G.P.': [955, 2259, 3331], 'Bartunik': [956, 2260, 3332], '1997;': [961, 2265, 3337, 4968], '389:': [962, 2266, 3338], '77-81Crossref': [963, 2267, 3339], '(513)': [966, 2270, 3342], '12Tuuttila': [969], 'Morgunova': [971], 'Bergmann': [973], 'U.': [974], 'Lindqvist': [975], 'Tryggvason': [983], 'Schneider': [985], '284:': [991], '1133-1140Crossref': [992], '(81)': [995], 'TIMPs': [1003, 2198, 4287], '(N-TIMP)': [1004, 2177], '∼14': [1006], 'kDa': [1007], 'encompasses': [1009], 'two-thirds': [1012], 'molecule.': [1015, 2319], 'architecture': [1017], 'N-TIMP': [1019, 1780], 'β-barrel': [1024], 'scaffold,': [1025], 'reminiscent': [1026, 3551], 'oligosaccharide/oligonucleotide-binding': [1029], '(OB)': [1030], 'motif.': [1031], 'C-terminal': [1033, 3993, 4031, 4063, 4109, 4806], 'hand,': [1038, 2533, 3389, 3713], 'consists': [1039], 'mainly': [1040], 'β-sheets': [1042], 'structurally': [1045], 'less': [1046], 'well': [1047, 1875, 3372], 'defined.': [1048], 'three': [1051, 2704, 4346], 'disulfide': [1052, 3467], 'bonds': [1053], 'each': [1055, 1550, 2357], 'TIMP.': [1058], 'Mutagenesis': [1059, 1415], 'kinetic': [1061, 2399, 3414, 3628], 'analysis': [1062, 3415, 4940], 'full-length': [1065, 1434, 1608, 4046, 4074, 4088, 4120, 4130, 4776, 4788], 'forms': [1068, 1438, 2174, 3289, 4350, 4777], 'TIMP-1-3': [1070], 'showed': [1071, 2195, 3416], 'MMP-inhibitory': [1074], 'function': [1075], 'resides': [1078], 'exclusively': [1079], 'at': [1080, 1342, 1674, 1709, 1800, 2310, 2486, 2655, 2685, 2825, 2854, 2985, 3060, 3148, 3272, 3355, 3397, 3486, 4290], '(13Huang': [1084], 'Arumugam': [1090], 'Van': [1092], 'Doren': [1093], 'S.R.': [1094], 'FEBS': [1097], '384:': [1100], '155-161Crossref': [1101], '(97)': [1104], '14Murphy': [1107], 'Houbrechts': [1109], 'Cockett': [1111, 1132], 'M.I.': [1112, 1133], 'Williamson': [1113, 3069], "O'Shea": [1115, 1134], 'A.J.P.': [1118, 1137], '1991;': [1120], '30:': [1121], '8097-8102Crossref': [1122], '(285)': [1125], '15Nguyen': [1128], 'Q.': [1129, 4979], 'Willenbrock': [1130], '2089-2095Crossref': [1143], '(82)': [1146, 4973], '16Lee': [1149], 'M.H.': [1150, 1293, 1313, 1498, 1567], 'Becherer': [1153, 1296], 'J.D.': [1154, 1297], 'Biochem.': [1157, 1300, 1328], 'Biophys.': [1158, 1301], 'Res.': [1159, 1302, 1928, 4950, 5037], 'Commun.': [1160, 1303], '280:': [1162, 1305], '945-950Crossref': [1163, 1306], '(52)': [1166, 1309], 'Despite': [1169, 2924], 'fact': [1171, 4702], 'co-crystal': [1174], 'MT1-MMP/TIMP-2': [1177], 'has': [1178, 1285, 1890, 3483, 4111, 4929, 5145], 'available': [1180, 3623, 4307], 'some': [1182, 2120, 3305, 4704], 'time,': [1183, 2032], 'there': [1185, 1940, 2942], 'no': [1187, 1468, 1942, 2944, 2957, 3715, 4112], 'why': [1191, 3124], 'inhibiting': [1197], 'report': [1201], 'novel': [1203], 'strategy': [1204], 'adopted': [1205], 'our': [1207, 1289, 1385, 1563, 1975, 2006, 2137, 2168, 2299, 4266, 4488, 4556, 4772, 5117, 5168], 'laboratory': [1208, 1976], 'approaching': [1210], 'conundrum.': [1212], 'succeeded': [1214, 4001], 'identifying': [1216, 4003], 'By': [1226], 'exchanging': [1227], 'these': [1228, 2311, 2359, 2386, 5121], '“obstructive”': [1229], 'created': [1237, 1423, 2651, 2684, 3351, 3407], 'N-TIMP-1': [1239, 1528, 1587, 1595, 1656, 2484, 2731, 2767, 3732, 3964, 4095, 4610, 4732], 'exhibited': [1242, 2716], 'Materials—All': [1251], 'chemicals': [1252], 'reagents': [1254], 'were': [1255, 1270, 1340, 1422, 1431, 1487, 1523, 1552, 1614, 1707, 1717, 1776, 1855, 2388, 2405, 2683, 3193, 3219, 3269, 3350, 3684, 3828, 4698, 5085], 'purchased': [1256], 'Sigma': [1258], 'unless': [1259], 'otherwise': [1260], 'stated.': [1261], 'Restriction': [1262], 'enzymes': [1263, 2213, 4874], 'Vent': [1265, 1427], 'DNA': [1266, 1428], 'polymerase': [1267], 'PCRs': [1269], 'obtained': [1271], 'New': [1273], 'England': [1274], 'Biolabs.': [1275], 'fluorometric': [1277, 1798], 'substrate': [1278], 'assay': [1282, 1347, 1640, 1799], '(QF-24:': [1283], 'Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2)': [1284], 'described': [1287, 1383, 1495], 'previous': [1290, 1386, 1564, 4264], 'papers': [1291, 2895], '(16Lee': [1292], '17Lee': [1312], 'Verma': [1314], 'Nath': [1318], 'Dodds': [1322, 1503, 1572], 'P.': [1323, 1504, 1573], '364:': [1331], '227-234Crossref': [1332], '(40)': [1335], 'Kinetic': [1338, 2411], 'assays': [1339], 'performed': [1341, 1708, 1777], '27': [1343, 1710, 1801], '°C': [1344, 1711, 1802], 'fluorescence': [1346], 'buffer': [1348], '(10': [1349], 'mm': [1350, 1353], 'CaCl2,': [1351], '50': [1352], 'Tris-HCl,': [1354], 'pH': [1355], '7.5,': [1356], '0.05%': [1357], 'Brij-35,': [1358], '1%': [1359], 'Me2SO,': [1360], '0.02%': [1361], 'NaN3)': [1362], 'PerkinElmer': [1365], 'Life': [1366], 'Sciences': [1367], '50B': [1368], 'spectrofluorimeter': [1369], 'equipped': [1370], 'thermostatic': [1372], 'cuvette': [1373], 'holders.': [1374], 'expressed,': [1378], 'refolded,': [1379], 'purified': [1381], 'paper': [1387, 1565, 5134], '(18Will': [1388], 'Butler': [1392], 'G.S.': [1393], '17119-17123Abstract': [1403], '(506)': [1411], 'Site-directed': [1414], 'N-TIMP-1—TIMP-1': [1417], 'mutants': [1418, 1486, 1596, 1781, 2404, 2682, 2705, 2747, 2970, 3228, 3245, 3260, 3349, 3632, 3694, 3827, 3965, 5084, 5119], 'work': [1421, 2425, 4833, 5165], 'PCR': [1425], 'using': [1426, 1795, 1813], 'polymerase.': [1429], 'Mutations': [1430], 'incorporated': [1432], 'human': [1440], 'cDNAs': [1442], '(in': [1443], 'pRSET-c': [1444], 'Escherichia': [1445], 'coli': [1446, 1491], 'expression': [1447], 'vector,': [1448], 'Invitrogen)': [1449], 'either': [1451, 2371, 2674, 4809], 'forward': [1452], 'or': [1453, 2375, 2676, 2893, 3797, 4567, 4649, 4685, 4811], 'reverse': [1454], 'primers,': [1455], 'depending': [1456, 1664, 2379], 'locations.': [1459], 'All': [1460, 1715], 'constructs': [1461], 'sequenced': [1464], 'confirm': [1466, 3103], 'unwanted': [1469], 'had': [1471], 'introduced': [1473, 4041], 'during': [1474], 'mutagenesis': [1476, 2409, 2424, 2696, 4559], 'process.': [1477, 2410], 'Protein': [1478, 1507, 1576, 4966], 'Refolding': [1479], 'Assessment': [1481], 'Activity': [1483], 'Titration—N-TIMP-1': [1485], 'expressed': [1488], 'refolded': [1493, 1524], 'previously': [1496], '(19Lee': [1497, 1566], 'Sci.': [1508, 1577, 1914, 4223, 4996, 5023], '11:': [1510, 1579], '2493-2503Crossref': [1511, 1580], '(28)': [1514, 1583], 'Full-length': [1517], 'V4A/P6V/T98L': [1521, 1612, 3831, 3870, 3932, 3996, 4103, 4121, 4152, 4780, 4800], 'essentially': [1525, 4738], 'exception': [1531, 1591, 3614, 5079], '0.5': [1533], 'm': [1534], 'arginine': [1535], 'included': [1537, 3360], 'refolding': [1540], 'buffer.': [1541], 'concentration': [1543, 1695], 'preparation': [1551], 'assessed': [1553], 'determined': [1555, 1636], 'titration': [1557], 'MMP-2': [1559, 1623, 5089], 'Scholar)': [1585, 3101], 'engineering.': [1588], 'With': [1589, 3612], 'T98F,': [1593, 5081], 'all': [1594, 2033, 3621, 5082], 'retained': [1597], 'full': [1598], 'MMP-2,': [1602, 1618], 'irrespective': [1603], 'loci.': [1606], 'Refolded': [1607], 'highly': [1615, 4826, 5086], 'association': [1620, 2452, 2502, 2549, 3895, 3942, 3958, 4126, 4159, 4818], 'rates': [1621], '(k': [1624, 1771, 2454, 2512, 3900, 3914], 'on)': [1625, 2455], 'being': [1626, 2473, 3657, 3697, 3938, 4370], 'over': [1627], '10': [1628, 2515], '-8m-1': [1629], 's-1.': [1630], 'amount': [1632], 'T98F': [1634], 'Bio-Rad': [1638], 'kit.': [1641], 'Inhibition': [1642], 'Constant': [1643, 1769], 'Measurement': [1644, 1770], 'iapp': [1646, 1735, 2471, 2496, 2725, 2740, 2931, 2934, 3232, 3430, 3515, 3526, 3650, 3675, 3874, 3885, 3891, 3934, 4119], ')—MT1-MMP': [1647], '(0.15': [1648], 'nm)': [1649, 1783, 2936, 3235, 3439, 3517, 3656, 3696, 3876, 3887], 'pre-incubated': [1651], 'increasing': [1653], 'concentrations': [1654], 'mutants,': [1657, 2941, 3739], 'ranging': [1658, 3366], '0': [1660, 1744, 1825], '500': [1662, 3438], 'nm,': [1663], 'inhibitors.': [1670, 4877], 'Incubation': [1671], 'allowed': [1673], 'room': [1675], 'temperature': [1676], '3': [1678], 'h': [1679], 'before': [1680, 3464, 4333, 4429], 'steady': [1681, 1804, 1833], 'state': [1682, 1805, 1834], '(V': [1683], 's)': [1684], 'measurement.': [1685], 'Quenched': [1686], 'fluorescent': [1687], 'peptide': [1688], 'QF-24': [1689, 5184], 'added': [1691], 'final': [1694], '1': [1697, 2978], 'μm': [1698], 'initiate': [1700], 'assays.': [1702], 'Measurements': [1703], 'activities': [1706, 4198], 'throughout': [1712, 2407], 'work.': [1714], 'data': [1716, 3212], 'fitted': [1718], 'competitive': [1720], 'equations': [1723], 'computer': [1726], 'program': [1727], 'Grafit': [1728], 'obtain': [1730], 'estimation': [1732], 'K': [1734, 2470, 2930, 3525, 3649], 'values': [1736, 1854, 2472], 'Equation': [1738, 1814], '1,': [1739], 'Vs=(V0/2Et)×(Et-It-Kiapp)+(Kiapp+It-Et)2+4EtKiapp)1/2)(Eq.': [1740], '1)': [1741, 3830], 'where': [1742, 1818], 'V': [1743, 1824, 1830, 4144], 'rate': [1747, 1790, 1843, 2453, 2550, 3896, 3959, 4127, 4160, 4819], 'absence': [1750], 'inhibitor;': [1752], 'E': [1753], 't': [1754], 'total': [1757, 1764], 'concentration;': [1759, 1823], 'It': [1761, 3596], 'concentration.': [1766], 'Association': [1767], 'Rate': [1768], ')—k': [1773], 'measurements': [1775], 'adding': [1779], '(3-50': [1782], '(0.05': [1787], 'nm).': [1788, 2498, 2742, 3680, 3893, 3940, 4098, 4123], 'inhibition': [1792, 2545, 2758, 3741, 3954, 4117, 4155], 'followed': [1794, 2736], 'continuous': [1797], 'until': [1803], 'reached.': [1807], 'progress': [1809], 'curve': [1810], 'analyzed': [1812], '2,': [1815], 'P=Vst+(V0-Vs)(1-e-kt)/k(Eq.': [1816], '2)': [1817, 3835], 'p': [1819], 'product': [1822], 'initial': [1828], 'velocity;': [1829, 1835], 's': [1831], '=': [1832], 'k': [1837, 1852, 1861], 'apparent': [1840, 3716, 3740, 4154], 'order': [1842], 'constant': [1844, 2448, 2546, 2759, 3742, 3955, 4156], 'equilibrium': [1846], 'between': [1847, 1945, 2064, 2828, 2999, 4527], 'complex.': [1851], 'calculated': [1856], 'linear': [1858], 'regression': [1859], 'concentrations.': [1864], 'Strategy': [1865], 'Mutagenesis—Although': [1868], 'conserved': [1876, 4347, 4432], 'both': [1878], 'primary': [1879, 2149], 'conformation,': [1882], 'inability': [1884, 1961], 'long': [1893], 'standing': [1894], 'conundrum': [1895], 'engineers': [1898, 4252], 'interested': [1899, 3194], 'mechanism': [1902, 4259, 5172], 'TIMP-MMPs': [1904], '(20Baker': [1906], 'A.H.': [1907, 4216], 'Edwards': [1908, 4217], 'D.R.': [1909, 4218], 'Cell': [1913, 4222], '115:': [1916, 4225], '3719-3727Crossref': [1917, 4226], '(973)': [1920, 4229], '21Nagase': [1923], 'Arthritis': [1927, 4949], 'Ther.': [1929, 4951], '4:': [1931, 4953], '51-61Crossref': [1932, 4954], '(48)': [1934, 4956], 'First': [1937, 3850], 'foremost,': [1939], 'obvious': [1943], 'contrast': [1944], 'amino': [1947, 2377, 2393, 3143, 3361, 3607, 3624, 3668, 3725, 4368, 4620, 4628, 4920, 5096], 'acid': [1948, 3144], 'distribution': [1949], 'account': [1958], '(Fig.': [1965, 2296, 2353, 2647, 2678, 2839, 2867, 3401, 3489, 3558, 4379, 4409, 4442, 4467], '1).': [1966, 2648, 2679, 2868, 3490, 4410], 'Hypothetical': [1967], 'docking': [1968], 'models': [1973], 'failed': [1978, 4310], 'reveal': [1980], 'significant': [1981, 2958], 'interfacial': [1982, 4525], 'clashes': [1983], 'satisfactorily': [1986, 4837], 'explain': [1987, 3123], 'lack': [1989, 2052, 3137], 'ability': [1991], 'binary': [1997], 'challenging': [2003], 'aspect,': [2004], 'view,': [2007, 2138], 'although': [2010, 2888], 'structures': [2012, 3284, 4309], 'delineated': [2021], 'crystallography': [2026, 2194], 'considerable': [2029], 'length': [2030], 'hypotheses': [2035], 'regarding': [2036], 'inactivity': [2038, 4248], 'remained': [2043], 'speculative.': [2045], 'Taken': [2046, 4822], 'together,': [2047, 4823], 'propose': [2049], 'due': [2060], 'simple': [2062], 'incompatibility': [2063], 'topology': [2067], 'molecules.': [2071], 'Instead,': [2072], 'believe': [2074], 'inducing': [2081, 3304], 'conformational': [2082, 2128, 3207, 3308], 'changes': [2083, 2129, 2959, 3208], 'isomerization': [2087], 'process': [2088], 'needs': [2090], 'overcome': [2093], 'enzyme-inhibitor': [2096], '(EI)': [2097], 'formation': [2099, 2754], '(22Morrison': [2100], 'J.F.': [2101], 'Walsh': [2102], 'C.T.': [2103], 'Enzymol.': [2105], '1995;': [2106], '248:': [2107], '201-301Google': [2108], 'reason': [2111], 'this,': [2113], 'hypothesize,': [2115], 'presence': [2118], '“obstructive': [2121], 'epitope(s)”': [2122], 'prevent': [2124], 'These': [2133, 2368], 'obstructive': [2134, 2302, 3588, 4005, 4274], 'epitope(s),': [2135], 'must': [2139], 'rather': [2141, 2313, 4925], 'subtle': [2142], 'readily': [2146], 'identifiable': [2147], 'sequence': [2150], 'alignment': [2151, 2998], 'examination.': [2154], 'Hence,': [2155, 2649, 3154, 3345, 3799, 4469], 'approach': [2157], 'problem': [2159, 4767], 'precise': [2162], 'manner,': [2163], 'decided': [2165], 'confine': [2167], 'investigation': [2169], 'Structural': [2185], 'delineation': [2186], 'stromelysin-1·TIMP-1': [2188], 'MT1-MMP·TIMP-2': [2190, 3040, 4416, 4497], 'complexes': [2191, 2541, 4867], 'x-ray': [2193], 'inserting': [2202], '“MMP-binding': [2204], 'ridge”': [2205], 'site': [2209], 'grooves': [2210], 'This': [2273, 4381, 5133], 'MMP-binding': [2274, 2327], 'ridge,': [2275], 'large,': [2278], 'composed': [2280], 'N': [2284, 2708, 2830, 4891], 'terminus,': [2285, 4892], 'AB-loop,': [2287, 4894], 'CD-loop': [2289, 3255, 3264], 'EF-loop': [2292, 3442, 3458], 'molecule': [2295, 3204, 4495], '2).': [2297, 2354, 2840, 2980], 'In': [2298, 2355, 2482, 2499, 2857, 4319, 4679, 4782], 'opinion,': [2300], 'epitope(s)': [2303], 'more': [2305, 2884, 3781], 'likely': [2306], 'located': [2309, 2824, 4428], 'loci': [2312], 'than': [2314, 2467, 3531, 3700, 3783, 4082, 4139], 'OB-core': [2316], 'Based': [2320], 'hypotheses,': [2323], 'divided': [2325], 'ridge': [2328], 'five': [2332], '“divisions,”': [2333], '“N': [2336], 'terminus”': [2337], 'division,': [2338, 2341, 2344, 2347], '“Pro6”': [2340], '“AB-loop”': [2343], '“CD-loop”': [2346], 'finally': [2349], '“EF-loop”': [2351], 'division': [2352, 2710], 'turn,': [2356], 'divisions': [2360], 'sub-divided': [2362], 'independent': [2364], 'entities': [2365], 'termed': [2366, 2599], '“epitopes.”': [2367], 'multiple': [2376, 3826], 'acids,': [2378, 3625], 'locus.': [2382, 2856], 'Systematically,': [2383], 'residues': [2384, 2595, 2618, 2670, 2861, 3175, 3268, 4359, 4447, 4687], 'constituting': [2385], 'swapped': [2389], 'corresponding': [2392, 2669, 2860, 3492], 'acids': [2394, 3362, 3608, 3669, 3726, 4369, 4621, 4629, 5097], 'TIMP-2-4,': [2396, 2858, 2922], 'profiles': [2400, 3550, 3570, 3629, 5115], 'monitored': [2406], 'Analysis': [2412], 'Wild': [2414], 'N-TIMP-1-4': [2416, 2439], 'Catalytic': [2419], 'Domain': [2420, 3994], 'MT1-MMP—Before': [2422], 'any': [2423, 3172, 4393, 4934], 'out,': [2428], 'started': [2430], 'examining': [2432], 'affinities': [2435, 2466, 4572], 'shown': [2457, 2698, 3634, 3846], 'Table': [2459, 2700, 3636, 3848, 4054, 4603], 'I.': [2460], 'Clearly,': [2461], 'N-TIMP-2-4': [2462], 'far': [2464, 2900, 2987, 4944], 'superior': [2465, 2507, 4792], 'N-TIMP-1,': [2468, 2529, 3786, 4787], '0.3': [2478], '1.5': [2480], 'nm.': [2481], 'comparison,': [2483], 'least': [2487], '2': [2488], 'orders': [2489], 'magnitude': [2491], 'higher': [2492], 'value': [2494, 2932, 3527, 3651], '178': [2497, 2733, 4097], 'term': [2500], 'rate,': [2503, 3943], 'N-TIMP-2': [2504, 3883], 'slightly': [2506, 3220, 3685, 4137, 4812], 'N-TIMP-3': [2509, 2520, 3889, 3911], 'N-TIMP-4': [2511], 'N-TIMP-2,': [2514, 3795], '×': [2516, 2524, 3903, 3917, 4133], '10-5m-1': [2517, 2525, 3904, 3907, 3918, 4134], 's-1,': [2518, 3908], '-4,': [2522], '3-6': [2523, 3916], 's-1)': [2526, 3905, 4135], '(Table': [2527, 3236, 3440, 3518, 3735, 3951, 4143], 'I).': [2528], 'establishing': [2538, 4018], 'MT1-MMP.Table': [2543, 2756], 'IApparent': [2544], '(Kiapp)': [2547, 2760, 3743, 3956, 4157], '(kon)': [2551, 3960, 4161], 'N-TIMP-1-4Wild': [2557], 'typeKi': [2558], 'app': [2559, 2769, 3746, 3969, 4164], '(×': [2560, 2563, 3747, 3970, 3973, 4165, 4168], '10−9m)k': [2561, 3971, 4166], '10−5m−1s−1)N-TIMP-1178': [2564], '±': [2565, 2567, 2569, 2571, 2573, 2575, 2577, 2773, 2775, 2777, 2780, 2782, 2784, 2787, 2790, 2792, 2794, 2798, 2800, 2802, 2804, 2806, 2808, 2810, 2813, 3749, 3751, 3753, 3755, 3757, 3759, 3761, 3763, 3765, 3976, 3978, 3980, 3982, 4171, 4174, 4176], '20NAN-TIMP-21.30': [2566], '0.1310.1': [2568], '3.8N-TIMP-31.38': [2570], '0.066.04': [2572], '0.70N-TIMP-40.30': [2574], '0.023.25': [2576], '0.35': [2578], 'Open': [2579, 2815, 3767, 3984, 4178], 'table': [2580, 2816, 3768, 3985, 4179], 'new': [2583, 2819, 3771, 3988, 4182], 'tab': [2584, 2820, 3772, 3989, 4183], 'Mutants—The': [2586, 2966, 3256, 3443], 'side': [2587, 3004, 4375, 4655], 'chains': [2588, 3005], 'second': [2591, 2631, 3466, 3802], 'fourth': [2594, 2662, 3257], '(also': [2598], 'P1′': [2600], 'P3′': [2602], 'subunits)': [2603], 'critically': [2605, 4612], 'important': [2606, 3271], 'determination': [2609], 'dock': [2619], 'directly': [2620, 4589], 'S1′': [2623], 'S3′': [2625], 'pockets': [2627], 'MMPs.': [2629], 'residue': [2632, 2663, 2875, 3059, 3107, 3411, 3493, 3589, 4396, 4539, 4564, 4586, 4927], '-3': [2636], 'TIMP-2': [2642, 3111, 3215, 3925, 4403, 4494, 4756], '-4': [2644, 3182, 3913], 'serine': [2646, 2675, 2915, 4568], 'one': [2653, 3404, 5153], 'position': [2657], 'Thr2': [2659], '(T2S).': [2660], 'valine.': [2667], 'Therefore,': [2680], 'locus,': [2687], 'V4S': [2689, 2738], 'V4A.': [2691], 'results': [2693, 3841, 4050], 'II.': [2701], 'terminus': [2709, 2831], '(T2S,': [2711], 'V4A,': [2712], 'V4S),': [2714], 'V4A': [2715, 3855, 4720], 'substantial': [2717], 'improvement': [2718], 'affinity': [2721, 2962, 3225, 3426, 3507, 3688, 3730, 3861, 3867, 3930, 4068, 4081, 4730, 4816], '66': [2726], 'nm': [2727, 3433, 4093], 'versus': [2728, 4094], 'nm),': [2734], 'closely': [2735, 3909], '81': [2741], 'Nonetheless,': [2743], 'none': [2744, 2889, 3242], 'potentiating': [2751], 'IIApparent': [2757], 'generation': [2766], 'mutantsKi': [2768], '(×10−9': [2770], 'M)N-terminal': [2771], 'mutantsT2S220': [2772], '20V4A66': [2774], '6V4S81': [2776], '24Pro6': [2778], 'mutantsP6V78': [2779], '4P6S95': [2781], '5P6A165': [2783], '13AB-loop': [2785], 'mutantsT2-AB-loop77': [2786], '6Long': [2788], 'T2-AB-loop117': [2789], '18T3-AB-loop106': [2791], '7T4-AB-loop170': [2793], '13CD': [2795], 'loop': [2796, 2836], 'mutantsM66K462': [2797], '103M66D>500M66L237': [2799], '18M66I146': [2801], '10M66V183': [2803], '13M66A199': [2805], '20M66G254': [2807], '28V69L259': [2809], '30EF-loop': [2811], 'mutantsT98L11.1': [2812], '1.6': [2814], 'Pro6': [2821, 2871, 2911, 2953, 4550], 'Mutants—Pro6': [2822], 'junction': [2827], 'α-helix': [2835], 'unique': [2843, 4544], 'it': [2845, 4059, 4824], 'valine,': [2863, 4639], 'serine,': [2864, 3709], 'Substitution': [2869, 4561], 'smaller': [2874], 'might': [2876, 4065, 4907], 'arguably': [2877], 'release': [2878], 'constraints': [2880], 'bring': [2882], 'about': [2883, 5102], 'relaxed': [2885], 'local': [2886], 'dynamics,': [2887], 'published': [2898], 'so': [2899, 4943], 'emphasized': [2902, 4932], 'significance': [2904, 4245], 'residue.': [2907], 'mutated': [2910, 3618], '(P6V),': [2914], '(P6S),': [2916], '(P6A)': [2919], 'mimic': [2921], 'respectively.': [2923], '2-fold': [2926], 'reduction': [2927], '78-95': [2935], 'P6V': [2938, 3857, 4722], 'P6S': [2940], 'manifestation': [2945], 'inhibition.': [2949, 3254, 3611, 3824], 'Surprisingly,': [2950], 'replacement': [2951, 3499], 'produced': [2956, 3641, 3714], 'AB-loop': [2965, 2974, 3065, 3178, 3201, 3926], 'next': [2967, 3664], 'set': [2968], 'centered': [2971], 'around': [2972], '(Figs.': [2977], 'cavity': [2984, 3050], '“left”': [2988], 'edge': [2989], 'molecule,': [2992], 'result': [2994], 'strategic': [2997], 'MT-loop': [3001], 'Asp212,': [3007], 'Ser189,': [3008], 'Phe180': [3010], 'Crystal': [3037], '(Protein': [3042, 3292, 4324, 4418, 4498], 'Data': [3043, 3293, 4325, 4419, 4499], 'Bank': [3044, 3294, 4326, 4420, 4500], 'code': [3045, 4327, 4421, 4501], '1BUV)': [3046, 4422, 4502], 'shows': [3047, 4268, 4424], 'functions': [3051], 'receptacle': [3054], 'Tyr-36,': [3056], 'conspicuous': [3058], 'tip': [3062, 3150], 'TIMP-2.': [3067], '(23Williamson': [3072], 'Hutton': [3074], 'Vogt': [3076], 'Rapti': [3078], '32966-32970Abstract': [3091], '(35)': [3099], 'did': [3102, 3121, 3945], 'Tyr-36': [3106], 'crucial': [3109], 'establish': [3113], 'TIMP-3': [3125, 3180, 3217], 'TIMP-4': [3127], 'equally': [3129], 'good': [3130], 'despite': [3134], 'complete': [3136, 4659], 'tyrosine': [3140, 3683, 4670], '(or': [3141], 'similar': [3146, 4632, 4675], 'nature)': [3147], 'AB-loop.': [3153], 'grafting': [3158], 'entire': [3160], 'AB-loops': [3161, 3218], 'onto': [3164], 'find': [3169, 3601], 'if': [3171], 'interact': [3184], 'MT1-loop': [3187], '“receptacle”': [3188], 'Rather,': [3191], 'finding': [3196], 'whether': [3198], '“obstructs”': [3202], 'indicated': [3213], 'beneficial': [3221, 4113], 'enhancing': [3223], '77-106': [3234], 'II': [3237, 3519], 'Fig.': [3239, 3521, 4146], '3).': [3240], 'Disappointingly,': [3241], 'considered': [3248, 3270, 4541], 'group': [3258], 'consisted': [3261], 'mutants.': [3265], 'Only': [3266], 'site,': [3274], 'Met-66': [3276, 3300, 3354], 'Val-69.': [3278], 'know': [3280], 'free': [3286], 'TIMP-1-bound': [3288], 'stromelysin-1': [3291, 3311, 4321], 'codes': [3295], '1QIA': [3296], '1UEA)': [3298], 'degree': [3306], 'change': [3309], '(11Gomis-Rüth': [3312], 'series': [3347, 3448], 'replace': [3353, 3409], 'site.': [3357], 'mutations': [3359, 3422, 4044, 4723], 'different': [3364], 'characteristics,': [3365], 'acidic': [3368, 4681], 'basic': [3370, 4686], 'hydrophobic': [3375, 4395, 4645], 'nature': [3377, 4634, 5093], '(M66K,': [3378], 'M66D,': [3379], 'M66L,': [3380], 'M66I,': [3381], 'M66V,': [3382], 'M66A,': [3383], 'M66G).': [3385], 'On': [3386], 'given': [3390], 'Val-69': [3399], 'locus': [3400, 3488], '1),': [3402], '(V69L).': [3412], 'Subsequent': [3413, 4099, 4796], 'majority': [3419], 'impaired': [3424, 3728, 3928], '146': [3432], 'excess': [3436], 'II).': [3441], 'last': [3444, 4343], 'Thr98': [3451, 3460, 3576, 3583, 3619, 3707, 4270, 4282, 4329, 4362, 4378, 4383, 4406, 4508, 4518, 4534, 4624, 5083], '(T98L)': [3455], 'division.': [3459], 'situated': [3462, 4331], 'right': [3463, 4332], 'bond': [3468], '(Cys3-Cys99)': [3469], 'TIMP-1.': [3471, 4240, 4546], 'Interestingly,': [3472], 'leucine.': [3497], 'vastly': [3504], '11': [3516], '4).': [3522, 3559], '16-fold': [3529], 'lower': [3530, 4138], 'N-TIMP-1.': [3537, 3722], 'striking': [3540, 4915], 'effect': [3541, 3645, 3717, 4745], 'T98L': [3545, 3563, 3778, 3864, 4764], 'clearly': [3547, 4761], 'manifested': [3548], 'Throughout': [3560, 4694], 'series,': [3562], 'exhibiting': [3568], 'akin': [3571], 'N-TIMP-2-4.': [3575, 4743], 'Point': [3577], 'Mutants—So': [3578], 'far,': [3579, 3998], 'identified': [3582, 4710], 'key': [3587, 4903], 'renders': [3591, 4277], 'would': [3597], 'interesting': [3599], 'effects': [3604, 3821, 4028, 4114], 'cysteine,': [3616], 'III.': [3637], 'Not': [3638, 4184], 'surprisingly,': [3639], 'isoleucine': [3640, 4598], 'same': [3643, 4749], 'potentiation': [3644], 'leucine,': [3647, 4636], 'T98I': [3653], '(12': [3655], 'T98L.': [3662], 'methionine': [3673], 'T98V': [3676], 'T98M': [3678], '∼30': [3679], 'Glutamine': [3681], 'poorer,': [3686], 'T98Q': [3691], 'T98Y': [3693], '(90-120': [3695], 'marginally': [3698, 4791], 'better': [3699, 4080], 'protein.': [3704], 'Replacement': [3705], 'remaining': [3724], 'severely': [3727], 'III).Table': [3736], 'IIIThr98': [3737], 'point': [3738], 'MT1-MMPKi': [3745, 4163], '10−9m)SmallT98G>1000T98A>1000NucleophilicT98S181': [3748], '17HydrophobicT98V30.7': [3750], '1.6T98I12.0': [3752], '0.8T98M27.1': [3754], '1.5T98P>1000AromaticT98F>1000T98Y119': [3756], '13T98W>1000AcidicT98D>1000T98E597': [3758], '37AmideT98N237': [3760], '12T98Q94': [3762], '6BasicT98H530': [3764], '40T98K>1000T98R>1000': [3766], 'Combination': [3773], 'Good': [3775], 'Epitopes—Even': [3776], 'though': [3777, 4665], 'much': [3780], 'still': [3790], '-3,': [3796], '-4.': [3798], 'phase': [3803], 'work,': [3806, 4696], 'combined': [3808, 3967], 'major': [3812], 'positive': [3813, 4708], 'attempt': [3817], 'study': [3819, 4267, 4513, 4797], 'Two': [3825], 'made:': [3829], 'mutant,': [3833, 4104, 4153, 4801], 'V4A/P6V/TIMP-2': [3836, 3936], 'AB-loop/T98L': [3837, 3937], 'quadruple': [3838], 'mutant.': [3839, 3865, 4781], 'combination': [3844], 'IV.': [3849], 'all,': [3852], 'incorporation': [3853, 3922], 'significantly': [3858, 3927, 4079], 'improved': [3859, 4569], '1.66': [3875], 'practically': [3878], 'equal': [3879, 4739], '1.30': [3886], '1.38': [3892], '1.48': [3902], 'exceeded': [3906], 'resembling': [3910], 's-1).': [3919], 'Unexpectedly,': [3920], '5.2': [3939], 'however,': [3944, 4105, 4802], 'seem': [3947, 4386], 'affected': [3950], 'IV).Table': [3952], 'IVApparent': [3953], 'epitopesKi': [3968], '10−5m−1s−1)Combined': [3974], 'mutantsV4A/P6V/T98L1.66': [3975], '0.121.48': [3977], '0.35V4A/P6V/T2-AB-loop/T98L5.22': [3979], '0.201.45': [3981], '0.14': [3983], 'Effects': [3990], 'Activity—So': [3997], 'hinder': [4014], 'What': [4025, 4241, 4912, 5101], 'association?': [4035], 'address': [4037], 'issue,': [4039], 'V4A/': [4042], 'P6V/T98L': [4043], 'summarized': [4052], 'At': [4056], 'sight,': [4058], 'appeared': [4060], 'improve': [4066], 'counterpart': [4085], 'iapp,': [4087], '91': [4092], 'comparison': [4100, 4783], '1.86': [4122], 'Furthermore,': [4124], '(0.9': [4132], 'version': [4142], '5).Table': [4147], 'VFull-length': [4148], 'wild-type': [4149], '10−5m−1s−1)Wild-type': [4169], 'TIMP-190.6': [4170], '5.4NAFull-length': [4172], 'V4A/P6V/T98L1.86': [4173], '0.170.89': [4175], '0.09': [4177], 'they': [4193], 'modulate': [4195], 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[4341], 'histidines': [4348], 'zinc-binding': [4353, 4437], 'ligands.': [4354], 'Distance-wise,': [4355], 'MMP-3': [4358], 'closest': [4360, 4448, 4885], 'Pro221,': [4366], '∼4': [4371], 'Å': [4372], 'chain': [4376, 4656], '6).': [4380, 4443, 4468], 'aside,': [4382], 'close': [4390], 'contact': [4391, 4526], 'particular': [4394], 'stromelysin-1.': [4401], 'Leu100': [4408, 4426, 4450], 'again': [4423, 4769], 'third': [4431], 'histidine': [4433], '(His249)': [4434], 'motif': [4438], '(HEXXHXXGXX': [4439], '249)': [4441], 'His249': [4452], 'Pro259,': [4454], 'almost': [4455], 'spitting': [4457], 'image': [4458], 'setting': [4461], 'found': [4462], 'TIMP-1·MMP-3': [4464], 'mentioned': [4465, 4548, 5073], 'above': [4466], '“His249/Pro259': [4472], 'pair”': [4473], 'deciding': [4478], 'factor': [4479], 'rejection': [4482], 'TIMP-1?': [4484], 'part': [4486], 'modeling': [4489], 'simulation,': [4490], 'replaced': [4492], 'bearing': [4506], 'mutation.': [4511, 4765], 'suggests': [4514, 4583, 4803], 'substitution': [4516], 'enhance': [4523], '(not': [4532], 'shown).': [4533], 'earlier,': [4549], 'featured': [4553], 'prominently': [4554], 'list': [4557], 'study.': [4560], 'significantly.': [4575], 'Yet': [4576], 'again,': [4577], 'examination': [4578], 'stromelysin-1/TIMP-1': [4581], 'association.': [4593], 'Why': [4594], 'should': [4595], 'best': [4601, 4627], 'residues?': [4602], 'III': [4604], 'demonstrates': [4605], 'dependent': [4613], 'biophysical': [4616], 'occupying': [4622, 5098], 'isoleucine,': [4638], 'methionine.': [4641], 'Too': [4642], 'bulky': [4643], '(tryptophan': [4646], 'phenylalanine)': [4648], 'minute': [4650], '(glycine': [4651], 'alanine)': [4653], 'resulted': [4657], 'abrogation': [4660], 'activity.': [4662], 'Strangely,': [4663], 'even': [4664], 'phenylalanine': [4666], 'tolerated,': [4669], 'beneficial,': [4672], 'notwithstanding': [4673], 'size': [4676], 'phenylalanine.': [4678], '(aspartate': [4682], 'glutamate)': [4684], '(lysine': [4688], 'arginine)': [4690], 'tolerated.': [4693], 'intrigued': [4699], 'individual': [4707], 'always': [4713], 'mutually': [4714], 'complementary': [4715], 'hoped.': [4717], 'Incorporation': [4718], 'T98L,': [4725], 'example,': [4727], 'level': [4737], 'additive.': [4747], 'said': [4753], 'AB-loop;': [4757], 'incompatible': [4762], 'highlighted': [4770], 'binding.': [4795], 'inert': [4810], 'detrimental': [4813], 'unlikely': [4827], 'explained': [4836], 'steric': [4839], 'reasons': [4840], 'alone.': [4841], 'true': [4843], 'answer,': [4844], 'believe,': [4846], 'lies': [4847], 'dynamics': [4851], 'governs': [4857], 'course': [4859], 'interaction.': [4862], 'Crystallographic': [4863], 'MMP·TIMP': [4866], 'portray': [4869], 'static': [4870], 'representations': [4871], 'Undeniably,': [4878], 'parts': [4880], 'intimacy': [4886], 'CD-loop.': [4897], 'Here,': [4898], 'TIMP/MMPs': [4905], 'fact,': [4909], 'lie': [4910], 'elsewhere.': [4911], 'acid,': [4921], 'Thr98,': [4922], '“insignificant”': 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