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2680, 2746], 'conflicting': [40, 302, 1173], 'theories': [41, 76, 303, 338], 'proposed': [42, 304, 1144, 1177], 'that': [43, 79, 101, 169, 201, 228, 305, 341, 363, 431, 463, 490, 1044, 1178, 1251, 1334, 1350, 1386, 2921, 3054, 3156, 3217, 3269, 3347, 3593, 3679, 3695, 3871, 3898, 4067, 4114, 4170], 'due': [44, 117, 306, 379, 3020, 3977], 'inhibitor-resistant': [47, 309, 693, 1194], 'activity': [48, 310, 874, 1196, 1338, 2218, 2342, 2431, 2457, 3004, 3018, 3780], 'mesotrypsin': [49, 80, 106, 138, 145, 175, 311, 342, 368, 400, 407, 437, 687, 769, 900, 1040, 1072, 1166, 1182, 1252, 1324, 2377, 2784, 2793, 2922, 2963, 3147, 3162, 3189, 3223, 3239, 3275, 3348, 3425, 3463, 3479, 3505, 3547, 3560, 3584, 3599, 3620, 3680, 3782, 3885, 4115, 4127, 4171, 4183], 'could': [50, 312, 1391, 3092], 'prematurely': [51, 313], 'activate': [52, 314, 1199, 3277, 3429, 3482], 'degrade': [54, 316, 1201, 3563, 3682, 4186], 'zymogens': [56, 318, 1204, 3279, 3436, 3567], 'and': [57, 142, 158, 214, 319, 404, 420, 476, 547, 566, 573, 590, 644, 700, 702, 764, 1099, 1108, 1262, 1320, 1370, 1429, 1448, 1505, 1527, 1552, 1562, 1572, 1578, 1687, 1713, 1746, 1835, 1846, 1857, 1861, 1903, 2038, 2054, 2066, 2073, 2216, 2231, 2329, 2391, 2419, 2499, 2502, 2527, 2581, 2596, 2620, 2670, 2725, 2732, 2778, 2792, 2892, 2959, 3061, 3085, 3088, 3133, 3236, 3283, 3378, 3432, 3446, 3471, 3536, 3635, 3685, 3722, 3789, 3993, 4018, 4027, 4040, 4054, 4081, 4130], 'thus': [58, 320, 3237, 3723], 'play': [59, 321, 3287], 'pathogenic': [61, 323], 'protective': [63, 211, 325, 473, 1402], 'role': [64, 326, 1145, 1266, 1322, 1380, 3289, 3582], 'in': [65, 86, 91, 191, 206, 258, 327, 348, 353, 453, 468, 520, 596, 603, 622, 647, 688, 696, 708, 740, 775, 804, 823, 911, 1051, 1059, 1183, 1267, 1325, 1476, 1524, 1549, 1766, 1823, 2031, 2249, 2320, 2382, 2517, 2546, 2564, 2606, 2638, 2679, 2715, 2727, 2752, 2853, 2965, 2973, 3012, 3036, 3067, 3185, 3257, 3290, 3351, 3411, 3423, 3585, 3650, 3699, 3800, 3803, 3872, 3892, 3908, 3949, 4004, 4009, 4068, 4136, 4162], 'pancreatitis.': [67, 221, 329, 483], 'the': [69, 92, 102, 125, 134, 148, 153, 161, 170, 186, 196, 199, 207, 217, 229, 241, 331, 354, 364, 387, 396, 410, 415, 423, 432, 448, 458, 461, 469, 479, 491, 503, 536, 550, 577, 765, 806, 824, 859, 884, 935, 955, 1035, 1045, 1054, 1060, 1067, 1096, 1112, 1115, 1120, 1127, 1143, 1157, 1162, 1184, 1193, 1258, 1301, 1313, 1326, 1342, 1351, 1365, 1394, 1401, 1530, 1697, 1716, 1742, 1757, 1862, 1904, 1916, 1922, 1933, 1939, 1948, 1994, 2000, 2021, 2024, 2081, 2186, 2198, 2222, 2241, 2285, 2318, 2352, 2360, 2366, 2379, 2415, 2428, 2451, 2455, 2472, 2513, 2560, 2688, 2698, 2708, 2745, 2788, 2820, 2865, 2931, 2934, 2944, 2961, 2967, 3002, 3010, 3015, 3025, 3028, 3032, 3037, 3055, 3068, 3082, 3097, 3157, 3164, 3175, 3193, 3197, 3222, 3254, 3267, 3291, 3518, 3552, 3566, 3594, 3613, 3631, 3643, 3693, 3700, 3716, 3728, 3779, 3784, 3804, 3873, 3888, 3903, 3982, 3991, 3994, 4000, 4010, 4036, 4069, 4073, 4120], 'present': [70, 332, 1314, 4023], 'study': [71, 333, 1315, 3819], 'we': [72, 334, 1316, 1332, 1348, 3215, 3265, 3777, 3795], 'ruled': [73, 335], 'out': [74, 336, 2635, 3579], 'both': [75, 337], 'by': [77, 339, 535, 816, 1257, 1341, 1399, 1467, 1538, 1554, 1840, 2064, 2071, 2303, 2309, 2762, 2863, 3059, 3095, 3253, 3281, 3343, 3420, 3532, 3539, 3642, 3654, 3706, 3715], 'demonstrating': [78, 340], 'was': [81, 115, 343, 377, 706, 735, 773, 1176, 1248, 1339, 1407, 1412, 1422, 1435, 1452, 1465, 1501, 1506, 1522, 1547, 1655, 1673, 1694, 1750, 1764, 1866, 1893, 1906, 1925, 1936, 1944, 1997, 2084, 2154, 2189, 2219, 2244, 2271, 2307, 2343, 2363, 2432, 2515, 2539, 2562, 2599, 2633, 2677, 2759, 3019, 3034, 3048, 3057, 3148, 3163, 3340, 3349, 3426, 3488, 3529, 3542, 3807, 4049, 4057, 4172], 'grossly': [82, 344], 'defective': [83, 345, 3350], 'not': [84, 346, 1375, 3045, 3062, 3226, 3481, 3562, 3704, 3947, 4058, 4185], 'only': [85, 347, 1376, 2999, 3227, 3705, 4044], 'binding,': [88, 350], 'but': [89, 351, 1383, 3044, 3231, 3541, 3713, 3955, 3976], 'also': [90, 352, 1249, 1384, 3203, 3232, 3714], 'activation': [93, 203, 242, 257, 355, 465, 504, 519, 860, 1180, 1366, 1388, 2981, 3029, 3501, 3519, 3614, 3698, 3729, 3805, 3826], 'degradation': [95, 178, 357, 440, 1327, 3023, 3056, 3098, 3785, 3821, 3952], 'zymogens.': [98, 360, 3689], 'We': [99, 361, 2956, 3895], 'found': [100, 362, 695, 1333, 2972], 'restricted': [103, 365], 'ability': [104, 366, 4164], 'bind': [108, 370], 'hydrolyze': [112, 374], 'protein': [113, 375, 1106, 3130, 3229, 3234, 3603], 'substrates': [114, 376, 2225, 3604], 'solely': [116, 378], 'single': [120, 382, 3168, 4016, 4083, 4187], 'evolutionary': [121, 383, 1343, 3169, 3194], 'mutation,': [122, 384], 'changed': [124, 386], 'serine-protease': [126, 388], 'signature': [127, 389], 'glycine': [128, 390], '198': [129, 391], 'residue': [130, 392, 1050, 3179], 'arginine.': [132, 394], 'Remarkably,': [133, 395], 'same': [135, 397], 'mutation': [136, 398], 'endowed': [137, 399, 1340], 'with': [139, 401, 771, 811, 1105, 1471, 1540, 1675, 1826, 1895, 1908, 2034, 2049, 2273, 2314, 2346, 2376, 2407, 2434, 2464, 2507, 2554, 2612, 2622, 2668, 2787, 2801, 2986, 3138, 3180, 3809, 4014], 'novel': [141, 403, 813, 863], 'unique': [143, 405, 1319, 3158], 'function:': [144, 406], 'rapidly': [146, 408], 'hydrolyzed': [147, 409], 'reactive-site': [149, 411], 'peptide': [150, 412, 808, 3615, 3890, 3900, 3984, 4002, 4122], 'bond': [151, 413, 3891, 3901, 3985, 4003], 'Kunitz-type': [154, 416, 936], 'SBTI,': [157, 419, 2454], 'irreversibly': [159, 421], 'degraded': [160, 422], 'Kazal-type': [162, 424, 956], 'temporary': [163, 425], 'SPINK1.': [165, 427, 1405], 'The': [166, 428, 524, 568, 895, 1373, 1460, 1891, 1912, 1990, 2178, 2238, 3153, 4110], 'observations': [167, 429, 1374, 3345], 'suggest': [168, 430, 1385], 'function': [172, 434, 870, 1164, 3443], 'digestive': [177, 439], 'inhibitors.': [181, 194, 443, 456, 1330, 3152], 'This': [182, 444, 3209, 3247, 3338, 3690, 4056], 'mechanism': [183, 254, 445, 516, 3285], 'can': [184, 446, 1197, 3276, 3638, 3681], 'facilitate': [185, 447], 'digestion': [187, 449, 1268, 3998], 'foods': [189, 451], 'rich': [190, 452], 'Furthermore,': [195, 457, 1111, 1331, 3590, 3970], 'findings': [197, 459, 3416], 'raise': [198, 460], 'possibility': [200, 462], 'inappropriate': [202, 464, 3696], 'mesotrypsinogen': [205, 244, 256, 467, 506, 518, 585, 734, 803, 1358, 1390, 1693, 1934, 1995, 2079, 2183, 2193, 2676, 2741, 2983, 3472], 'pancreas': [208, 470, 526, 739, 1185, 3701], 'might': [209, 471, 867, 1186, 1253, 3286], 'lower': [210, 472], 'SPINK1': [212, 474, 1521, 1561, 2306, 2373, 2550, 3141], 'levels': [213, 475, 583, 1403], 'contribute': [215, 477, 1392], 'development': [218, 480, 3292], 'this': [223, 485, 862, 1335, 2947, 3258, 3284, 3457, 3636, 3775, 3899, 3944], 'regard,': [224, 486], 'it': [225, 487, 1175, 2702, 2917], 'noteworthy': [227, 489], 'well': [230, 492], 'known': [231, 493], 'pathological': [232, 494], 'trypsinogen': [233, 249, 495, 511, 594, 1575, 1919, 1955, 2693, 2712, 2774, 3380, 3469, 3684, 3697, 3820, 3825, 3910, 4022, 4048, 4085], 'activator': [234, 496], 'cathepsin': [235, 497, 1355, 1653, 1671], 'B': [236, 498, 1356, 1654, 1672, 4053], 'exhibited': [237, 499, 2794, 3474], 'preference': [239, 501], 'all': [246, 508], 'three': [247, 509, 528], 'isoforms,': [250, 512, 571, 3634], 'suggesting': [251, 513], 'biochemical': [253, 515], 'acinar': [260, 522], 'cells.': [261, 523], 'secretes': [527], 'isoforms': [529], 'trypsinogen,': [531, 563, 565, 575, 581, 1571, 3721], 'are': [533, 557, 2723, 2734], 'encoded': [534, 815], 'PRSS': [537], '(protease,': [538], 'serine)': [539], 'genes': [540], 'PRSS1': [541], '(OMIM': [542, 545], '276000),': [543], 'PRSS2': [544], '601564),': [546], 'PRSS3.': [548], 'On': [549], 'basis': [551, 2866], 'their': [553, 2753, 4163], 'electrophoretic': [554, 2597], 'mobility,': [555], 'they': [556], 'commonly': [558], 'referred': [559, 849], 'cationic': [562, 572, 1369, 1518, 1570, 1954, 2773, 2808, 3117, 3377, 3433, 3449, 3493, 3513, 3534, 3788, 3893, 3909, 4131, 4167, 4192], 'anionic': [564, 574, 1371, 1574, 2771, 2810, 3119, 3379, 3431, 3451, 3495, 3790], 'mesotrypsinogen.': [567], 'major': [570, 3632], 'constitute': [576], 'bulk': [578], 'secreted': [580, 1918, 2696], 'whereas': [582, 3486], 'were': [586, 1536, 1576, 1830, 1838, 1848, 2029, 2062, 2069, 2195, 2374, 2401, 2505, 2529, 2552, 2588, 2610, 2750, 2785, 3111, 3417, 3502, 3521], 'reported': [587, 1566, 1581], 'between': [588, 3990], '3': [589], '10%': [591, 2625], 'total': [593], 'content': [595], 'normal': [597], 'juice': [599], '(see': [600, 908], 'Table': [601, 645, 909], 'I': [602, 646], 'Ref.': [604, 623, 648, 912, 2639, 4137], '1.Rinderknecht': [605], 'H.': [606, 625, 650, 670, 711, 914, 971, 1206, 1273, 3297, 3356, 3659, 3732], 'Renner': [607, 626, 653, 671, 712, 915, 972, 1207, 1274, 3298, 3357, 3660, 3733], 'I.G.': [608, 627, 654, 672, 713, 916, 973, 1208, 1275, 3299, 3358, 3661, 3734], 'Carmack': [609, 630, 673, 716, 919, 976, 1211, 1278, 3302, 3361, 3664, 3737], 'C.': [610, 631, 674, 717, 878, 920, 977, 1212, 1279, 1295, 3303, 3362, 3665, 3738], 'Gut.': [611], '1979;': [612], '20:': [613], '886-891Crossref': [614], 'PubMed': [615, 639, 661, 725, 759, 793, 842, 928, 985, 1007, 1028, 1089, 1220, 1242, 1287, 1489, 1595, 1613, 1629, 1646, 1736, 1795, 1813, 1886, 1969, 1985, 2102, 2118, 2146, 2173, 2494, 2659, 2887, 2912, 3311, 3333, 3370, 3404, 3673, 3746, 3768, 3839, 3863, 3930, 4105, 4157], 'Scopus': [616, 640, 662, 726, 760, 794, 843, 929, 986, 1008, 1029, 1090, 1221, 1243, 1288, 1490, 1596, 1614, 1630, 1647, 1737, 1796, 1814, 1887, 1970, 1986, 2103, 2119, 2147, 2174, 2660, 2888, 2913, 3312, 3334, 3371, 3405, 3674, 3747, 3769, 3840, 3864, 3931, 4106, 4158], '(71)': [617], 'Google': [618, 642, 664, 728, 762, 796, 845, 931, 988, 1010, 1031, 1092, 1223, 1245, 1290, 1492, 1598, 1616, 1632, 1649, 1739, 1798, 1816, 1889, 1972, 1988, 2105, 2121, 2149, 2176, 2495, 2662, 2890, 2915, 3314, 3336, 3373, 3407, 3676, 3749, 3771, 3842, 3866, 3933, 4108, 4160], 'Scholar;': [619, 643], 'Fig.': [620, 3013, 3412, 3868, 4134], '8': [621], '2.Rinderknecht': [624, 913], 'Abramson': [628, 714, 917, 974, 1209, 1276, 3300, 3359, 3662, 3735], 'S.B.': [629, 715, 918, 975, 1210, 1277, 3301, 3360, 3663, 3736], 'Gastroenterology.': [632, 718, 921, 978, 1213, 1280, 3304, 3363, 3666, 3739], '1984;': [633, 719, 922, 979, 1214, 1281, 3305, 3364, 3667, 3740], '86:': [634, 720, 923, 980, 1215, 1282, 3306, 3365, 3668, 3741], '681-692Abstract': [635, 721, 924, 981, 1216, 1283, 3307, 3366, 3669, 3742], 'Full': [636, 722, 754, 756, 925, 982, 1002, 1004, 1217, 1237, 1239, 1284, 1608, 1610, 1808, 1810, 1964, 1966, 2097, 2099, 2141, 2143, 2491, 2654, 2656, 2882, 2884, 3308, 3328, 3330, 3367, 3399, 3401, 3670, 3743, 3763, 3765, 3858, 3860, 3925, 3927, 4100, 4102, 4152, 4154], 'Text': [637, 723, 755, 757, 926, 983, 1003, 1005, 1218, 1238, 1240, 1285, 1609, 1611, 1809, 1811, 1965, 1967, 2098, 2100, 2142, 2144, 2492, 2655, 2657, 2883, 2885, 3309, 3329, 3331, 3368, 3400, 3402, 3671, 3744, 3764, 3766, 3859, 3861, 3926, 3928, 4101, 4103, 4153, 4155], 'PDF': [638, 724, 758, 927, 984, 1006, 1219, 1241, 1286, 1612, 1812, 1968, 2101, 2145, 2493, 2658, 2886, 3310, 3332, 3369, 3403, 3672, 3745, 3767, 3862, 3929, 4104, 4156], '(107)': [641, 727, 930, 987, 1222, 1289, 3313, 3372, 3675, 3748], '3.Rinderknecht': [649], 'Stace': [651], 'N.H.': [652], 'Dig.': [655], 'Dis.': [656], 'Sci.': [657], '1985;': [658], '30:': [659], '65-71Crossref': [660], '(67)': [663], 'Scholar).': [665, 729, 797, 846, 894, 1032, 1093, 1246, 1311, 1493, 1650, 1817, 1890, 1989, 2150, 2177, 2496, 3337, 3408, 3772, 3867, 3934, 4109], 'Rinderknecht': [666, 3655], 'et': [667, 3656], 'al.': [668, 3657], '(4.Rinderknecht': [669], 'Friedman': [675], 'R.': [676], 'Koyama': [677], 'P.': [678], 'Clin.': [679], 'Res.': [680, 1484, 1624, 1980, 2113], '1978;': [681], '26:': [682, 1734, 1793], '112AGoogle': [683], 'Scholar)': [684, 1740, 2891, 3374, 3677, 4161], 'first': [685], 'discovered': [686], '1978': [689], 'new': [692, 2855], 'protease': [694, 963, 1354, 2381], 'tissue': [699], 'fluid,': [701], 'systematic': [704], 'characterization': [705], 'published': [707], '1984': [709], '(2.Rinderknecht': [710, 970, 1205, 1272, 3296, 3355, 3658, 3731], 'A': [730, 2777, 4026], 'cDNA': [731], 'coding': [732], 'cloned': [736], 'from': [737, 1409, 1413, 1423, 1436, 1454, 1502, 1659, 1696, 1704, 1921, 2080, 2185, 2197, 2744, 3824], '1997': [741], '(5.Nyaruhucha': [742, 2870], 'C.N.M.': [743, 991, 1226, 2871, 3317, 3752], 'Kito': [744, 992, 1227, 2872, 3318, 3753], 'M.': [745, 993, 1228, 1588, 1601, 1619, 1621, 1637, 1639, 1661, 1801, 1879, 1957, 1975, 1977, 2090, 2108, 2110, 2166, 2479, 2484, 2643, 2647, 2873, 3319, 3754, 3830, 3832, 3847, 3851, 3914, 3918, 4089, 4093, 4141, 4145], 'Fukuoka': [746, 994, 1229, 2874, 3320, 3755], 'S.I.': [747, 995, 1230, 2875, 3321, 3756], 'J.': [748, 782, 787, 834, 996, 1017, 1022, 1078, 1083, 1231, 1602, 1641, 1802, 1958, 2091, 2135, 2485, 2648, 2876, 2901, 2906, 3322, 3393, 3757, 3834, 3852, 3919, 4094, 4146], 'Biol.': [749, 789, 997, 1024, 1085, 1232, 1603, 1803, 1959, 2092, 2136, 2486, 2649, 2877, 2908, 3323, 3394, 3758, 3853, 3920, 4095, 4147], 'Chem.': [750, 998, 1233, 1604, 1804, 1960, 2093, 2137, 2487, 2650, 2878, 3324, 3395, 3759, 3854, 3921, 4096, 4148], '1997;': [751, 999, 1234, 2879, 3325, 3760], '272:': [752, 1000, 1235, 2880, 3326, 3761], '10573-10578Abstract': [753, 1001, 1236, 2881, 3327, 3762], '(85)': [761, 1009, 1244, 2889, 3335, 3770], 'Scholar),': [763, 932, 2916], 'crystal': [766, 1037, 1160, 2894], 'structure': [767, 1038, 2895], 'complexed': [770], 'benzamidine': [772, 3102], 'solved': [774], '2002': [776], '(6.Katona': [777, 1073, 2896], 'G.': [778, 1013, 1074, 1586, 1877, 2128, 2130, 2132, 2164, 2645, 2897, 3386, 3388, 3390, 3849, 3916, 4091, 4143], 'Berglund': [779, 1014, 1075, 2898], 'G.I.': [780, 1015, 1076, 2899], 'Hajdu': [781, 1016, 1077, 2900], 'Gráf': [783, 1018, 1079, 2133, 2902, 3391], 'L.': [784, 786, 1019, 1021, 1080, 1082, 1721, 1780, 2124, 2134, 2903, 2905, 3382, 3392], 'Szilágyi': [785, 1020, 1081, 2904], 'Mol.': [788, 1023, 1084, 2907], '2002;': [790, 1025, 1086, 2651, 2909, 3855, 3922, 4097, 4149], '315:': [791, 1026, 1087, 2910], '1209-1218Crossref': [792, 1027, 1088, 2911], '(83)': [795, 1030, 1091, 2914], 'An': [798], 'alternatively': [799], 'spliced': [800], 'form': [801, 2718], 'signal': [807], 'replaced': [810, 3174, 3808], 'sequence': [814, 1914, 2180, 2868], 'alternative': [818], 'exon': [819], '1': [820, 1676, 2050, 2255, 2326, 2388, 2392, 2425, 2460, 2993, 3557, 3878, 4005, 4031], 'expressed': [822, 1523, 1548, 1577, 1765, 1920, 2184, 2678, 2958], 'brain': [826], '(7.Wiegand': [827], 'U.': [828], 'Corbach': [829], 'S.': [830, 1727, 1786], 'Minn': [831], 'A.': [832, 1725, 1784], 'Kang': [833], 'Müller-Hill': [835], 'B.': [836], 'Gene': [837], '(Amst.).': [838], '1993;': [839], '136:': [840], '167-175Crossref': [841], '(101)': [844], 'Although': [847], 'usually': [848], '"brain': [852], 'trypsinogen,"': [853], 'there': [854], 'no': [856, 1134, 1264, 2356, 3465, 3475], 'evidence': [857, 1043, 1137], 'chimeric': [864], 'molecule,': [865], 'have': [868, 1254, 2957], 'unrelated': [871], 'proteolytic': [873], '(8.Chen': [875], 'J.-M.': [876, 1293], 'Ferec': [877, 1294], 'Cooper,': [879, 1296], 'D.N.': [880, 1297], 'Nature': [881, 889, 1298, 1306], 'Encyclopedia': [882, 1299], 'Human': [885, 1302, 1520, 1543, 1651], 'Genome.': [886, 1303], 'Vol.': [887, 1304], '5.': [888, 1305], 'Publishing': [890, 1307], 'Group,': [891, 1308], 'London2003:': [892, 1309], '645-650Google': [893, 1310], 'most': [896, 3904], 'intriguing': [897], 'property': [898], 'polypeptide': [905], 'V': [910], '1The': [941], 'abbreviations': [942, 948], 'used': [943, 949, 2682, 3427, 3554, 3796], 'are:': [944, 950], 'SBTIsoybean': [945, 951], 'inhibitorTricineN-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine.1The': [947], 'inhibitorTricineN-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine.': [953], '(SPINK1,': [961], 'serine': [962, 2975], 'inhibitor,': [964], 'Kazal': [965], 'type': [966], '1,': [967, 2776], 'OMIM': [968], '167790)': [969], 'Scholar,': [989, 1011, 1224, 1291, 1599, 1617, 1633, 1799, 1973, 2106, 2122, 3315, 3750, 3843], '5.Nyaruhucha': [990, 1225, 3316, 3751], '6.Katona': [1012], 'Analysis': [1033], 'recent': [1036], 'provided': [1041], 'compelling': [1042], 'presence': [1046, 2932, 3038, 3069, 3595, 4070], 'arginine': [1049], 'place': [1052], 'highly': [1055], 'conserved': [1056, 3177], 'Gly198': [1057, 2969, 3178], '(Gly193': [1058], 'chymotrypsin': [1061, 1447, 2217], 'numbering': [1062], 'system)': [1063], 'responsible': [1065], 'Arg198': [1094, 2935, 3200, 3218, 3597], 'occupies': [1095], 'S2′': [1097], 'subsite': [1098], 'long': [1101], 'side-chain': [1102], 'sterically': [1103, 2939], 'clashes': [1104], 'possibly': [1109, 3686], 'substrates.': [1110], 'charge': [1113], 'guanidino': [1116], 'group': [1117], 'contributes': [1118], 'strong': [1121], 'clustering': [1122], 'positive': [1124], 'charges': [1125], 'around': [1126], 'primary': [1128], 'specificity': [1129], 'pocket': [1130], 'mesotrypsin.': [1132], 'However,': [1133, 2946, 4124], 'direct': [1135], 'experimental': [1136, 3607], 'ever': [1139], 'presented': [1141], 'Arg198.': [1147, 1346], 'N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine.': [1151, 1155], 'Despite': [1156], 'high': [1158, 1949, 3071], 'resolution': [1159], 'structure,': [1161], 'remained': [1168], 'mysterious.': [1169], 'clearly': [1172, 4112], 'theories,': [1174], 'premature': [1179, 1387], 'cause': [1187], 'protect': [1189], 'against': [1190, 3206], 'pancreatitis,': [1191], 'freely': [1198], 'other': [1202, 3687], 'It': [1247], 'suggested': [1250, 2920], '"abandoned': [1256], 'process': [1259], 'evolution,"': [1261], 'important': [1265], 'physiology': [1271], '8.Chen': [1292], 'identified': [1317], 'specific': [1321, 2469], 'distinctive': [1336], 'enzymatic': [1337], 'selection': [1344, 3195], 'Finally,': [1347, 2151, 3517], 'showed': [1349], 'lysosomal': [1352], 'cysteine': [1353], 'activated': [1357, 1674, 2761, 2783, 3531], 'at': [1359, 2201, 2246, 2258, 2338, 2397, 2403, 2410, 2421, 2531, 2590, 2766, 2824, 3076, 3943, 4041, 4173, 4181], 'higher': [1361, 2797], 'rate,': [1362], 'relative': [1363, 2806], 'trypsinogens.': [1372], 'indicate': [1377], 'physiological': [1379, 2989], 'mesotrypsin,': [1382, 2355, 3718], 'pathogenesis': [1395], 'pancreatitis': [1398, 3295], 'reducing': [1400], 'Materials—N-CBZ-Gly-Pro-Arg-p-nitroanilide': [1406], 'purchased': [1408, 1703], 'Sigma.': [1410], 'Suc-Ala-Ala-Pro-Phe-p-nitroanilide': [1411, 2232], 'Bachem': [1414], '(King': [1415], 'Prussia,': [1417], 'PA),': [1418], 'ultrapure': [1419], 'bovine': [1420, 1432, 1446, 1450, 1463, 1541, 2332, 2394, 2408, 2443, 2465, 2763, 3353, 3483, 3683], 'enterokinase': [1421, 2987, 3063], 'Biozyme': [1424], 'Laboratories': [1425, 1438], '(San': [1426], 'Diego,': [1427], 'CA),': [1428], 'reagent': [1430], 'grade': [1431], 'serum': [1433, 2333, 2395], 'albumin': [1434, 2334, 2396], 'Biocell': [1437], '(Rancho': [1439], 'Dominguez,': [1440], 'CA).': [1441], 'Bovine': [1442], 'chymotrypsinogen': [1443, 3354, 3484, 3500], 'A,': [1444, 3485], 'TLCK-treated': [1445], 'TPCK-treated': [1449], 'obtained': [1453, 3094], 'Worthington': [1455], 'Biochemical': [1456], 'Corp.': [1457], '(Lakewood,': [1458], 'NJ).': [1459, 1668], 'concentration': [1461, 1853, 2412, 2418, 2475], 'determined': [1466, 1537, 2220, 2345, 2786], 'active': [1468, 3089, 3224, 3491, 3629, 3711], 'site': [1469, 3225, 3806, 3907, 3945], 'titration': [1470, 1539], 'p-nitrophenyl-p′-guanidinobenzoate': [1472], '(Sigma)': [1473], 'described': [1475, 1777, 2087, 2349, 2637], '(9.Chase': [1477], 'Jr.,': [1478, 2483], 'T.': [1479], 'Shaw': [1480], 'E.': [1481, 1767, 2001, 2126, 2683, 3384], 'Biochem.': [1482, 1622, 1642, 1978, 2111, 3835], 'Biophys.': [1483, 1623, 1979, 2112], 'Commun.': [1485, 1625, 1981, 2114], '1967;': [1486], '29:': [1487], '508-514Crossref': [1488], '(781)': [1491], 'Soybean': [1494], '(Glycine': [1495], 'max)': [1496], '(Kunitz': [1499], 'type)': [1500], 'Fluka': [1503], '(93619),': [1504], 'further': [1507, 3251, 3725, 3951], 'purified': [1508, 1528, 1553, 1579, 2155, 2743, 2960], 'on': [1509, 1529, 1684, 2156, 2541, 2601, 2819, 3009, 3100, 3109, 3468, 3783], 'affinity': [1511, 1532, 1872, 2159, 3103], 'column': [1512, 1873, 1892, 2160], 'containing': [1513, 2521, 2567], 'immobilized': [1514], 'S200A': [1515, 1531], 'mutant': [1516, 2984, 3798], 'trypsin.': [1519, 1542, 3496], 'Saccharomyces': [1525], 'cerevisiae': [1526], 'column.': [1533, 3104], 'Inhibitor': [1534, 2298, 2370, 2857], 'concentrations': [1535, 2316, 3073], 'pro-elastase': [1544, 3525], 'II': [1545], '(ELA2A)': [1546], 'Escherichia': [1550], 'coli': [1551, 1768, 2002, 2684], 'ecotin-affinity': [1555], 'chromatography.': [1556], 'Details': [1557, 2729], 'expression': [1559, 1717, 1941, 1951, 2685, 2690, 2710, 2731, 2748], 'ELA2A': [1563], 'will': [1564, 3249], 'be': [1565, 3093, 3250, 3508, 3623, 3639], 'elsewhere.': [1567], 'Ecotin,': [1568], 'previously': [1582, 1778, 2088, 3897], '(10.Lengyel': [1583, 1874, 2161], 'Z.': [1584, 1635, 1875, 2162, 2641, 3828, 3845, 3912, 4087, 4139], 'Pál': [1585, 1876, 2163, 2644, 3848, 3915, 4090, 4142], 'Sahin-Tóth': [1587, 1638, 1878, 2165, 2646, 3831, 3850, 3917, 4092, 4144], 'Prot.': [1589, 1880, 2167], 'Expr.': [1590, 1881, 2168], 'Purif.': [1591, 1882, 2169], '1998;': [1592, 1883, 2170], '12:': [1593, 1884, 2171], '291-294Crossref': [1594, 1885, 2172], '(43)': [1597, 1888, 2175], '11.Sahin-Tóth': [1600], '2000;': [1605, 1626, 1961, 1982, 2094, 2115], '275:': [1606, 1962, 2095], '22750-22755Abstract': [1607, 1963, 2096], '(140)': [1615, 1971, 2104], '12.Sahin-Tóth': [1618, 1974, 2107], 'Tóth': [1620, 1636, 1976, 2109, 2642, 3829, 3846, 3913, 4088, 4140], '278:': [1627, 1983, 2116], '286-289Crossref': [1628, 1984, 2117], '(167)': [1631, 1987, 2120], '13.Kukor': [1634], 'Eur.': [1640, 3833], '2003;': [1643, 3836], '270:': [1644, 3837], '2047-2058Crossref': [1645, 3838], '(76)': [1648, 3841], 'recombinant': [1652, 2182, 2740], 'generous': [1657], 'gift': [1658], 'Paul': [1660], 'Steed': [1662], '(Research': [1663], 'Department,': [1664], 'Novartis': [1665], 'Pharmaceuticals,': [1666], 'Summit,': [1667], 'Before': [1669], 'use,': [1670], 'mm': [1677, 1856, 1897, 1910, 2051, 2228, 2234, 2256, 2327, 2389, 2523, 2569, 2583, 2994, 3558, 3879, 4006, 4032], 'dithiothreitol': [1678, 2524, 2584], '(final': [1679, 2525, 2558, 2585], 'concentration)': [1680, 2230], '30': [1682, 2618], 'min': [1683, 2337, 2426, 2461, 2595, 4043], 'ice.': [1685], 'Expression': [1686, 2664], 'Purification': [1688], 'Mesotrypsinogen—The': [1690], 'gene': [1691, 1935, 1996], 'encoding': [1692], 'PCR-amplified': [1695], 'IMAGE': [1698], 'clone': [1699], '2659811': [1700], '(GenBank™': [1701], 'AW182356,': [1702], 'Incyte': [1705], 'Genomics': [1706], 'Reagents': [1707], '&': [1708], 'Services,': [1709], 'St.': [1710], 'Louis,': [1711], 'MO)': [1712], 'ligated': [1714], 'into': [1715, 1999], 'plasmid': [1718, 1924, 1992, 2188], 'pTrap': [1719, 1923], '(14.Gráf': [1720, 1779], 'Craik': [1722, 1781], 'C.S.': [1723, 1782], 'Patthy': [1724, 1783], 'Roczniak': [1726, 1785], 'Fletterick': [1728, 1787], 'R.J.': [1729, 1788], 'Rutter': [1730, 1789], 'W.J.': [1731, 1790], 'Biochemistry.': [1732, 1791], '1987;': [1733, 1792], '2616-2623Crossref': [1735, 1794], '(138)': [1738, 1797], 'behind': [1741], 'alkaline': [1743], 'phosphatase': [1744], 'promoter': [1745], 'signal-sequence.': [1747], 'Mutation': [1748], 'R198G': [1749, 2962, 2985], 'introduced': [1751], 'via': [1752], 'oligonucleotide-directed': [1753], 'site-specific': [1754], 'mutagenesis,': [1755], 'using': [1756, 2204, 2221, 2261, 2288], 'overlap': [1758], 'extension': [1759], 'PCR': [1760], 'mutagenesis': [1761], 'method.': [1762], 'Mesotrypsinogen': [1763, 2758], 'SM138': [1769], '[F–,': [1770], 'araD139,': [1771], 'Δ(lac)U169,': [1772], 'relA,': [1773], 'rpsL,': [1774], 'phoR],': [1775], '15.Sahin-Tóth': [1800], '1999;': [1805], '274:': [1806], '29699-29704Abstract': [1807], '(45)': [1815], 'Typically,': [1818], '2.4-liter': [1819], 'cultures': [1820, 2028], 'SM138/pTrap': [1822, 2689], 'Luria-Bertani': [1824, 2032], 'medium': [1825, 2033], '100': [1827, 2035, 2522, 2582], 'μg/ml': [1828, 2036, 2040], 'ampicillin': [1829, 2037], 'grown': [1831, 2030, 2055], 'saturation': [1833], 'overnight': [1834], 'periplasmic': [1836, 2699], 'fractions': [1837], 'isolated': [1839, 2070], 'osmotic': [1841], 'shock.': [1842], 'Tris-HCl': [1843, 1898, 2252, 2323, 2385, 2570], '(pH': [1844, 1899, 2253, 2324, 2386, 2571, 2991, 3555], '8.0)': [1845], 'NaCl': [1847], 'added': [1849], 'final': [1852, 2229, 2235, 2511], '20': [1855, 1896], '0.2': [1858], 'm,': [1859], 'respectively,': [1860], '∼260': [1863], 'ml': [1864], 'periplasm': [1865], 'applied': [1867], 'directly': [1868], 'ecotin': [1871, 2158], 'washed': [1894], '8.0)/0.2': [1900], 'M': [1901], 'NaCl,': [1902], 'zymogen': [1905, 2153, 3588], 'eluted': [1907], '50': [1909], 'HCl.': [1911], 'propeptide': [1913, 2179], 'mature': [1917], 'Ile-Gln-Ala-Phe-Pro-Val-(Asp)4-Lys.': [1926], 'attempt': [1929], 'increase': [1931], 'yield,': [1932, 3084], 'transferred': [1937], 'pTrap-T7': [1940, 1991, 2187], 'plasmid,': [1942], 'originally': [1945], 'constructed': [1946], 'level': [1950], '(11.Sahin-Tóth': [1956, 2089], 'harboring': [1993], 'transformed': [1998], 'Rosetta(DE3)': [2003], 'strain': [2004, 2011], '(Novagen),': [2005], 'BL21(DE3)': [2009], 'derivative': [2010], 'carrying': [2012], 'chromosomal': [2014], 'copy': [2015], 'T7': [2017], 'RNA': [2018], 'polymerase': [2019], 'under': [2020, 2736, 2988, 3551], 'control': [2022], 'lacZ': [2025], 'promoter.': [2026], '50-ml': [2027], '34': [2039], 'chloramphenicol': [2041], 'OD600': [2044], 'nm': [2045, 2248, 2312], '0.5,': [2047], 'induced': [2048], 'isopropyl': [2052], '1-thio-β-galactopyranoside,': [2053], 'additional': [2058], '5': [2059, 2535, 2594], 'h.': [2060], 'Cells': [2061], 'harvested': [2063], 'centrifugation': [2065], 'inclusion': [2067, 2082, 2720, 3461], 'bodies': [2068, 2083], 'sonication': [2072], 'centrifugation.': [2074], 'vitro': [2076], 'refolding': [2077], 'accomplished': [2085], '16.Szilágyi': [2123], 'Kénesi': [2125, 3383], 'Katona': [2127, 3385], 'Kaslik': [2129, 3387], 'Juhász': [2131, 3389], '2001;': [2138, 3396], '276:': [2139, 3397], '24574-24580Abstract': [2140, 3398], '(89)': [2148, 3406], 're-folded': [2152], 'Met-Val-Pro-Phe-(Asp)4-Lys.': [2190], 'Concentrations': [2191], 'solutions': [2194], 'calculated': [2196], 'ultraviolet': [2199], 'absorbance': [2200], '280': [2202], 'nm,': [2203], 'theoretical': [2206], 'extinction': [2207], 'coefficient': [2208], '40,570': [2210], 'm–1': [2211], 'cm–1.': [2212], 'Protease': [2213], 'Activity': [2214], 'Assays—Trypsin': [2215], 'synthetic': [2223, 2821], 'chromogenic': [2224, 2789], 'N-CBZ-Gly-Pro-Arg-p-nitroanilide': [2226, 2347, 2823, 3110], '(0.1–0.14': [2227], '(0.15': [2233], 'concentration),': [2236, 2512, 2526, 2559], 'respectively.': [2237], 'release': [2239], 'yellow': [2242], 'p-nitroanilide': [2243], 'followed': [2245], '405': [2247], '0.1': [2250, 2321, 2383], 'm': [2251, 2322, 2384], '8.0),': [2254, 2325, 2387], 'CaCl2,': [2257, 2328, 2390], '22': [2259], '°C': [2260, 2533, 2592], 'Spectramax': [2263], 'Plus': [2264], '384': [2265], 'microplate': [2266, 2294], 'reader': [2267, 2295], '(Molecular': [2268, 2277, 2296], 'Devices).': [2269, 2297], 'Elastase': [2270], 'assayed': [2272], 'DQ-elastin': [2274], 'fluorescent': [2275, 2293], 'substrate': [2276, 2790, 2822, 3817], 'Probes,': [2278], 'EnzCheck': [2279], 'elastase': [2280], 'assay': [2281, 2368], 'kit)': [2282], 'according': [2283], "manufacturer's": [2286], 'instructions': [2287], 'SpectraMax': [2290], 'Gemini': [2291], 'XS': [2292], 'Assays—Tight-binding': [2299], 'inhibition': [2300], 'SBTI': [2304, 2441, 2456, 2474, 2503, 3139], 'measured': [2308, 2433], 'incubating': [2310], '15–50': [2311], 'given': [2315, 2735], '1.5': [2330], 'mg/ml': [2331, 2393], '10': [2336], 'room': [2339, 2422, 3077], 'temperature.': [2340], 'Residual': [2341], 'then': [2344], 'above.': [2350], 'With': [2351], 'exception': [2353], 'significant': [2357], 'dissociation': [2358], 'inhibitor-trypsin': [2361], 'complex': [2362], 'detectable': [2364, 3571], 'during': [2365, 3027], '1-min': [2367], 'time.': [2369], 'Degradation—SBTI': [2371], 'incubated': [2375, 2420], 'indicated': [2380, 2404, 3678, 4066], '37': [2398, 2996, 3883], '°C.': [2399], 'Aliquots': [2400], 'withdrawn': [2402], 'times,': [2405], 'mixed': [2406], 'slightly': [2413], 'above': [2414], 'initial': [2416], 'temperature': [2423, 3078], 'before': [2427], 'residual': [2429], 'N-CBZ-Gly-Pro-Arg-p-nitroanilide.': [2435], 'Because': [2436], 'association': [2437, 2449], 'cleaved': [2439, 3887], '("modified")': [2440], 'considerably': [2446], 'slower': [2447, 2768], 'than': [2448, 2770, 3512, 3630, 4179], 'intact': [2452], '("virgin")': [2453], 'detected': [2458], 'after': [2459], 'incubation': [2463], 'measure': [2470], 'virgin': [2473], '(17.Luthy': [2476], 'J.A.': [2477], 'Praissman': [2478], 'Finkenstadt': [2480], 'W.R.': [2481], 'Laskowski': [2482], '1973;': [2488], '248:': [2489], '1760-1771Abstract': [2490], 'Gel': [2497], 'Electrophoresis': [2498], 'Densitometric': [2500, 2629], 'Analyses—Trypsinogen': [2501], 'samples': [2504, 2528, 2551], 'precipitated': [2506, 2553], 'trichloroacetic': [2508, 2556], 'acid': [2509, 2557, 2627, 3171], '(10%': [2510], 'precipitate': [2514, 2561], 'dissolved': [2516, 2563], 'Laemmli': [2518], 'sample': [2519, 2565], 'buffer': [2520, 2566], 'heat-denatured': [2530, 2589], '95': [2532, 2591], 'min.': [2536], 'Electrophoretic': [2537], 'separation': [2538, 2598], 'performed': [2540, 2600, 3035], '13%': [2542], 'SDS-PAGE': [2543, 2603], 'mini': [2544, 2604], 'gels': [2545, 2605], 'standard': [2547], 'Tris-glycine': [2548], 'buffer.': [2549, 2608], '20%': [2555, 2573, 3000, 4045], '200': [2568], '6.8),': [2572], 'glycerol,': [2574], '2%': [2575], 'SDS,': [2576], '0.04%': [2577], 'Coomassie': [2578, 2613], 'Blue': [2579, 2615], 'G-250,': [2580], 'concentrations).': [2586], 'Samples': [2587], '16%': [2602], 'Tris-Tricine': [2607], 'Gels': [2609], 'stained': [2611], 'Brilliant': [2614], 'R': [2616], 'min,': [2619], 'destained': [2621], '30%': [2623], 'methanol,': [2624], 'acetic': [2626], 'overnight.': [2628], 'quantitation': [2630], 'bands': [2632], 'carried': [2634], '18.Kukor': [2640, 3844, 4138], '277:': [2652, 3856, 3923, 4098, 4150], '6111-6117Abstract': [2653, 3857, 3924, 4099, 4151], '(55)': [2661, 3865, 3932, 4107, 4159], 'Scholar.': [2663], 'Mesotrypsinogen,': [2666], 'Activation': [2667, 3066], 'Enterokinase,': [2669], 'Catalytic': [2671, 2780, 3105], 'Properties': [2672], 'Mesotrypsin—Recombinant': [2674], 'routinely': [2681], 'systems.': [2686], 'host/plasmid': [2691], 'system': [2692, 2711], 'constitutively': [2695], 'space': [2700], 'where': [2701], 'acquires': [2703], 'native': [2705], 'fold.': [2706], 'Rosetta(DE3)/pTrap-T7': [2709], 'produced': [2714], 'denatured': [2717], 'bodies,': [2721], 'solubilized': [2724], 'renatured': [2726], 'vitro.': [2728], 'purification': [2733], '"Experimental': [2737], 'Procedures."': [2738], 'Importantly,': [2739, 3550], 'preparations': [2742], 'bacterial': [2747], 'systems': [2749], 'indistinguishable': [2751], 'functional': [2754], 'properties': [2755], 'studied': [2756], 'here.': [2757], 'completely': [2760], 'enterokinase,': [2764, 3046], 'albeit': [2765], 'rate': [2769, 4037], '(Fig.': [2775, 3005, 3142, 3548, 4024, 4051, 4128], 'B).': [2779], 'parameters': [2781, 2815, 3106], 'N-CBZ-Gly-Pro-Arg-p-nitroanilide,': [2791], '∼3-fold': [2796], 'turnover': [2798], 'number': [2799], '(kcat)': [2800], 'comparable': [2803], 'Km': [2804], 'value': [2805], '(Table': [2812, 3121], 'I).Table': [2813], 'IKinetic': [2814], 'trypsins': [2818], '22°CKmkcatkcat/Kmμms-1m-1': [2825], 's-1PRSS115': [2826], '±': [2827, 2829, 2833, 2835, 2839, 2841, 2845, 2847], '150': [2828], '13.3': [2830], '×': [2831, 2837, 2843, 2849], '106PRSS211': [2832], '141': [2834], '13.7': [2836, 2848], '106PRSS322': [2838], '2148': [2840], '46.7': [2842], '106R198G10': [2844], '237': [2846], '106': [2850], 'Open': [2851], 'table': [2852], 'tab': [2856], 'Resistance': [2858], 'Is': [2861], 'Caused': [2862], 'Arg198—On': [2864], 'alignments': [2869], 'resistant': [2924, 3149, 3190, 3544], 'proteinaceous': [2926], 'because': [2929, 3270, 4063], 'side': [2936, 3201], 'chain,': [2937], 'impairs': [2940], 'binding': [2942], 'enzyme.': [2945, 3969], 'notion': [2948, 3248, 3592], 'never': [2950, 3972], 'tested': [2952, 3266, 3568], 'experimentally': [2953], 'so': [2954], 'far.': [2955], 'mutant,': [2964], 'characteristic': [2968], 'residue,': [2970], 'universally': [2971], 'chymotrypsin-like': [2974], 'proteases,': [2976], 'restored.': [2979], 'Surprisingly,': [2980], 'conditions': [2990, 3553], '8.0,': [2992, 3556, 3882], 'Ca2+,': [2995], '°C)': [2997, 3080, 3884], 'yielded': [2998], 'expected': [3003, 4011], '1A).': [3006], 'As': [3007, 3144, 3409], 'shown': [3008, 3410], 'gel': [3011], '1C,': [3014], 'loss': [3016], 'massive': [3022], 'R198G-zymogen': [3026], 'process.': [3030, 3458], 'When': [3031, 3497], 'reaction': [3033], 'SPINK1,': [3040, 3282, 3707], 'inhibited': [3042], 'R198G-mesotrypsinogen': [3047], 'quantitatively': [3049], 'converted': [3050], 'trypsin,': [3052, 3450, 3535, 3712], 'indicating': [3053, 3346], 'mediated': [3058], '(not': [3064, 3515], 'shown).': [3065, 3516], 'Ca2+': [3072, 3876, 4033, 4072], '(50': [3074], 'mm)': [3075], '(22': [3079], 'increased': [3081], 'eventually': [3086], 'pure': [3087], 'R198G-mesotrypsin': [3090, 3108, 3124, 3454, 3487], 'preparation': [3091], 'separating': [3096], 'products': [3099], 'essentially': [3112, 3489], 'identical': [3113], 'those': [3115], 'I).': [3122], 'Strikingly,': [3123], 'fully': [3125, 3418, 3640], 'regained': [3126], 'sensitivity': [3128], 'inhibitors,': [3132, 3192, 3230], 'formed': [3134], 'tight': [3135], 'inhibitory': [3136], 'complexes': [3137], '2).': [3143], 'expected,': [3145], 'wild-type': [3146, 3546], 'these': [3151, 3414, 3575, 3793], 'experiments': [3154, 3256, 3422, 3520, 3576, 3794], 'confirmed': [3155, 3419], 'result': [3165, 3948], 'amino': [3170], 'change,': [3172], 'small': [3176], 'bulky': [3182], 'Arg.': [3183], 'Notably,': [3184], 'addition': [3186, 3447], 'rendering': [3188], 'potentially': [3198], 'trypsin-sensitive': [3199, 3245], 'chain': [3202, 4017, 4021, 4047, 4080, 4084, 4188, 4191], 'stabilized': [3204], 'mesotrypsin(ogen)': [3205], 'autocatalytic': [3207], 'degradation.': [3208], 'apparent': [3210], 'paradox': [3211], 'resolved': [3213], 'if': [3214], 'assume': [3216], 'blocks': [3219], 'access': [3220], 'substrates,': [3235], 'renders': [3238, 3598], 'relatively': [3240], 'inactive': [3241], 'toward': [3242, 3602], 'own': [3244], 'sites.': [3246], 'explored': [3252], 'subsequent': [3255], 'report.': [3259], 'Cannot': [3261], 'Activate': [3262], 'Pancreatic': [3263], 'Zymogens—Next,': [3264], 'hypothesis': [3268], 'unopposed': [3280], 'theory': [3339], 'already': [3341], 'contradicted': [3342], 'sporadic': [3344], 'activating': [3352], '(16.Szilágyi': [3381], '3,': [3413], 'previous': [3415, 4064], 'our': [3421, 3591], 'trypsinogen.': [3434, 3791], 'Both': [3435], 'autoactivated': [3437], 'spontaneously': [3438], 'time,': [3445], 'markedly': [3455], 'enhanced': [3456], 'contrast,': [3460], 'had': [3464], 'appreciable': [3466], 'effect': [3467], 'activation,': [3470], 'itself': [3473], 'autoactivation': [3476], 'either.': [3477], 'Wild-type': [3478], 'did': [3480, 3561, 4184], 'rates': [3498], 'compared': [3503], 'quantitatively,': [3504], 'proved': [3506], '500–1000-fold': [3509], 'less': [3510, 3628, 4176], 'efficient': [3511], 'extended': [3522], '2': [3526], '(ELA2A),': [3527], 'efficiently': [3530], 'even': [3537], 'better': [3538], 'R198G-mesotrypsin,': [3540], 'totally': [3543], '3).': [3549], 'Ca2+),': [3559], 'any': [3564, 3950], 'extent.': [3572], 'Taken': [3573], 'together,': [3574], 'convincingly': [3577], 'rule': [3578], 'possible': [3581], 'promoting': [3586], 'intra-pancreatic': [3587], 'activation.': [3589], 'catalytically': [3600], 'impaired': [3601], 'gained': [3605], 'clear': [3606], 'support.': [3608], 'terms': [3610], 'cleaving': [3612, 4119, 4180], 'bonds': [3616], 'zymogens,': [3619], 'appears': [3621], '2–3': [3624], 'orders': [3625], 'magnitude': [3627], 'defect': [3637], 'repaired': [3641], 'restoration': [3644], 'Gly198.': [3646], 'Role': [3647], 'Trypsinogen': [3651], 'Degradation—Previous': [3652], 'work': [3653], 'observation': [3691], 'spawned': [3692], 'theory,': [3694], 'curbed': [3703], 'mops': [3709], 'up': [3710], 'SPINK1-resistant': [3717], 'eliminates': [3720], 'limits': [3724], 'escalation': [3726], 'cascade': [3730], 'To': [3773], 'test': [3774], 'model,': [3776], 'examined': [3778], 'For': [3792], 'activation-resistant': [3797], 'trypsinogens,': [3799], 'Lys-23': [3802], 'Gln': [3810], '(K23Q).': [3811], 'K23Q-trypsinogen': [3812, 4168], 'ideal': [3815], 'model': [3816], 'without': [3822], 'interference': [3823], '(13.Kukor': [3827], '4': [3869, 4135], 'shows': [3870], 'absence': [3874], '(in': [3877], 'EDTA,': [3880], 'pH': [3881], 'slowly': [3886], 'Arg122–Val123': [3889, 3983, 4001, 4121], 'K23Q-trypsinogen.': [3894], 'demonstrated': [3896], 'sensitive': [3905], 'trypsinolytic': [3906], '(18.Kukor': [3911, 4086], 'contrast': [3936], 'widely': [3939], 'held': [3940], 'belief,': [3941], 'cleavage': [3942, 3971], 'does': [3946], 'inactivation,': [3954], 'yields': [3956], 'double-chain': [3958, 3995], 'trypsin(ogen)': [3959], 'species,': [3960], 'functionally': [3963], 'equivalent': [3964], 'single-chain': [3967, 3992], 'parent': [3968], 'proceeds': [3973], 'completion,': [3975], 'trypsin-mediated': [3979], 're-synthesis': [3980], 'equilibrium': [3987, 4013, 4061, 4074], 'established': [3989], 'species.': [3996], 'Mesotrypsin-mediated': [3997], 'EDTA': [4007], 'resulted': [4008], 'hydrolysis': [4012], '∼18%': [4015], '82%': [4019], 'double': [4020, 4046, 4079, 4190], '4,': [4025, 4052], 'C).': [4028, 4055], 'Addition': [4029], 'significantly': [4034], 'decreased': [4035], 'cleavage,': [4039], '240': [4042], 'observed': [4050], 'true': [4060], 'yet,': [4062], 'studies': [4065], 'mixture': [4075], 'should': [4076], 'contain': [4077], '40%': [4078], '60%': [4082], 'results': [4111], 'demonstrate': [4113], 'capable': [4117], 'bond.': [4123], 'comparison': [4125], '4)': [4129], '(cf.': [4133], 'cleave': [4166], 'revealed': [4169], 'least': [4174], '500-fold': [4175], 'active.': [4177], 'Other': [4178], 'Arg122–Val123,': [4182], 'K23Q-tr': [4193]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2028307216', 'counts_by_year': [{'year': 2024, 'cited_by_count': 5}, {'year': 2023, 'cited_by_count': 3}, {'year': 2022, 'cited_by_count': 5}, {'year': 2021, 'cited_by_count': 7}, {'year': 2020, 'cited_by_count': 3}, {'year': 2019, 'cited_by_count': 3}, {'year': 2018, 'cited_by_count': 8}, {'year': 2017, 'cited_by_count': 5}, {'year': 2016, 'cited_by_count': 4}, {'year': 2015, 'cited_by_count': 5}, {'year': 2014, 'cited_by_count': 6}, {'year': 2013, 'cited_by_count': 8}, {'year': 2012, 'cited_by_count': 4}], 'updated_date': '2024-12-12T22:53:42.665045', 'created_date': '2016-06-24'}