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3513, 3525, 3528, 3588, 3596, 3601, 3618, 3629, 3636, 3640, 3647, 3650, 3664, 3681, 3685, 3690, 3703, 3706, 3790, 3804, 3822, 3826, 3829, 3931, 3941, 3966, 3990, 3994, 4035, 4039, 4053, 4058, 4065, 4077, 4087, 4097, 4104, 4121, 4124, 4128, 4153, 4179, 4189, 4209, 4213], 'active': [17, 203, 563, 1014, 1858, 3339], 'site': [18, 204, 564, 1015, 1859, 3812, 4042, 4100], 'Tyr-319': [19, 205], 'conserved': [22, 208, 468, 711, 785, 809, 874, 971, 1132, 1853, 3027, 4156], 'in': [23, 30, 39, 66, 111, 166, 209, 216, 225, 252, 297, 352, 413, 417, 561, 579, 645, 712, 756, 811, 818, 936, 979, 1012, 1129, 1137, 1302, 1348, 1407, 1562, 1712, 1856, 1872, 2113, 2413, 2523, 2554, 2558, 2637, 2641, 2653, 2672, 2684, 2719, 2722, 2736, 2753, 2771, 2780, 2795, 2804, 2810, 2848, 2967, 2987, 2992, 3077, 3150, 3595, 3635, 3653, 3659, 3663, 3679, 3759, 3803, 4034, 4127, 4137, 4157, 4174], 'type': [24, 31, 83, 108, 210, 217, 269, 294, 384, 713, 819, 1268, 1336, 1339, 1447, 1618, 1974, 2075, 2105, 2135, 2286, 2324, 2343, 2660, 2879, 2981, 3328, 3436, 4158, 4161], 'IA': [25, 211, 385, 820, 2979, 4159], 'sequences': [27, 213, 464, 2999], 'with': [28, 48, 70, 214, 234, 256, 410, 1026, 1209, 1213, 1327, 1351, 1412, 1428, 1456, 1470, 1488, 1496, 1522, 1637, 1724, 1760, 1851, 1897, 1978, 2038, 2202, 2313, 2346, 2415, 2461, 2483, 2657, 2667, 2738, 2846, 3156, 3215, 3275, 4141], 'counterparts': [29, 215], 'IIA': [32, 218, 714, 822, 4162], 'topoisomerases.': [34, 220, 387, 4163], 'Their': [35, 221], 'exact': [36, 222, 932, 1749, 2882], 'functional': [37, 160, 223, 346, 3766, 4150], 'roles': [38, 224, 412, 3758], 'catalysis': [40, 226, 3234], 'have': [41, 61, 227, 247, 804, 1089, 1174, 1987, 2334, 2547, 2757, 3252, 3468, 3756], 'not': [42, 124, 228, 310, 880, 946, 1823, 2178, 2425, 2717, 2802, 2836, 2962, 2975, 3605, 3626, 4046], 'been': [43, 229, 805, 1091, 1984, 3086], 'clearly': [44, 230, 4172], 'defined.': [45, 231], 'Mutant': [46, 232], 'enzymes': [47, 233, 391, 1342, 1826, 3005], 'two': [49, 235, 576, 1082, 1144, 2515, 2540, 3002, 3364], 'or': [50, 130, 236, 316, 974, 1083, 1202, 1448, 1619, 1716, 3144, 3396], 'more': [51, 237, 1084, 2463, 3371, 3677, 3714], 'these': [53, 88, 163, 239, 274, 349, 458, 557, 752, 872, 969, 1086, 1130, 3001, 3697], 'converted': [55, 241], 'to': [56, 60, 106, 153, 171, 242, 246, 292, 339, 357, 568, 574, 670, 807, 877, 994, 1184, 1231, 1330, 1659, 1746, 1829, 1986, 2317, 2354, 2676, 2766, 2829, 2895, 2902, 2914, 3011, 3025, 3146, 3272, 3319, 3453, 3502, 3521, 3524, 3532, 3607, 3628, 3655, 3809, 3821, 3940, 3989, 4095, 4114], 'alanines': [57, 243], 'were': [58, 244, 1199, 1207, 1262, 1300, 1343, 1386, 1494, 1520, 1534, 1575, 1595, 1708, 1766, 1827, 1864, 1888, 2307, 2411, 2506, 2518, 2531, 2543, 2844, 2961, 2974], 'found': [59, 245, 644, 817, 3024, 4072], '>90%': [62, 248, 1988], 'loss': [63, 143, 249, 329, 741, 1005, 1989, 3152, 3342, 3362, 3619], 'activity': [65, 251, 603, 884, 1106, 1149, 1347, 1871, 1952, 1992, 2053, 2069, 2087, 2131, 2176, 2219, 2246, 2266, 2287, 2428, 2745, 3260, 3315, 3409, 3472, 3505, 3517, 3712, 3891, 4013], 'relaxation': [68, 93, 102, 179, 254, 279, 288, 365, 744, 883, 1105, 1148, 1346, 1870, 1886, 1991, 2052, 2068, 2086, 2116, 2194, 2218, 2245, 2296, 2417, 2744, 3259, 3314, 3384, 3408, 3456, 3471, 3487, 3682, 3711, 3967, 4012, 4129], 'assay': [69, 255, 1024, 1180, 1501, 1893, 2762, 3683, 3688], '6': [71, 257, 1876, 2055, 2289, 3474], 'mm': [72, 258, 1028, 1360, 1365, 1398, 1416, 1422, 1472, 1480, 1564, 1627, 1877, 2056, 2126, 2189, 2255, 2282, 2290, 2485, 2623, 2665, 2678, 2698, 2790, 2853, 3285, 3448, 3475], 'Mg(II)': [73, 75, 104, 139, 146, 170, 259, 261, 290, 325, 332, 356, 446, 1009, 1029, 1119, 1145, 1591, 2064, 2208, 2278, 2351, 2401, 2408, 2435, 2452, 2470, 2551, 2706, 2711, 2715, 2741, 2791, 2825, 2854, 2991, 3269, 3309, 3346, 3365, 3378, 3405, 3445, 3449, 3478, 3497, 3624, 3656, 3760, 3771, 3788, 3807, 4177], 'present.': [74, 260], 'concentrations': [76, 262, 1117, 1493, 2633, 3310], '(15–20': [77, 263], 'mm)': [78, 264], 'inhibitory': [79, 265, 3324], 'for': [80, 91, 126, 131, 148, 162, 177, 266, 277, 312, 317, 334, 348, 363, 449, 599, 1093, 1107, 1120, 1147, 1255, 1333, 1345, 1381, 1464, 1485, 1540, 1577, 1590, 1671, 1690, 1869, 1901, 1955, 2088, 2129, 2132, 2181, 2309, 2624, 2645, 2689, 2725, 2746, 2906, 2944, 2990, 3075, 3221, 3312, 3325, 3373, 3383, 3407, 3507, 3516, 3617, 3965, 4152, 4198, 4206, 4222], 'wild': [82, 107, 268, 293, 1335, 1446, 1973, 2074, 2104, 2134, 2285, 2323, 2342, 2659, 2878, 3327, 3435], 'enzyme': [84, 109, 150, 270, 295, 336, 535, 1021, 2076, 2325, 2356, 2454, 2661, 2994, 3154, 3329, 3612, 3782, 4181], 'needed': [86, 272, 3964, 4197], 'by': [87, 116, 183, 273, 302, 369, 457, 984, 997, 1019, 1241, 1264, 1388, 1507, 1679, 1710, 1722, 1768, 1787, 1809, 1818, 1833, 1861, 2394, 2562, 2892, 3354, 3859], 'double': [89, 133, 275, 319, 1108, 1294, 1847, 1958, 1969, 2079, 2090, 2222, 2269, 2315, 2389, 2458, 2647, 2691, 3217, 3301, 3393, 3509, 3669, 3691], 'mutants': [90, 276, 1080, 1109, 1261, 1297, 1803, 1850, 1904, 1970, 2037, 2091, 2223, 2252, 2270, 2316, 2392, 2446, 2648, 2692, 2843, 3218, 3459, 3510, 3589, 3644], 'maximal': [92, 278, 1121, 2130, 2319, 3313], 'activity.': [94, 103, 280, 289, 1975, 2117, 3330, 3385, 3457, 3488, 3621, 4215], 'triple': [96, 128, 282, 314, 1079, 1296, 1849, 1963, 2081, 2184, 2391, 2727], 'mutant': [97, 129, 134, 283, 315, 320, 1341, 1449, 1620, 1959, 1977, 2185, 2259, 2459, 2728], 'D111A/D113A/E115A': [98, 284, 1962, 2183, 2421, 2842, 3643], 'had': [99, 285, 1971, 2049, 2210, 2433, 2467, 3480], 'no': [100, 286, 2050, 2668, 3469, 4011], 'detectable': [101, 115, 287, 301, 2051, 2561, 3470], 'binding': [105, 168, 291, 354, 1439, 2409, 2436, 2448, 2471, 2552, 2626, 2702, 2742, 2775, 3375, 3401, 3498, 3654, 3786, 3832, 3890, 3943, 3979, 4060, 4175], 'resulted': [110, 296, 748, 2112, 2636, 2794, 3149], 'an': [112, 298, 1551, 2214], 'altered': [113, 299, 1860], 'conformation': [114, 300], 'Glu-C': [117, 303, 1182, 1643, 1755, 2764, 2847, 2887, 2908, 3582, 3637, 3686, 3796, 4040, 4098, 4116], 'proteolytic': [118, 304, 1178, 2761, 2800], 'digestion.': [119, 305, 4117], 'This': [120, 306, 388, 2898, 3489, 3645, 3749], 'conformational': [121, 174, 307, 360, 1188, 2556, 2769, 3661, 3792, 4082, 4182, 4201], 'change': [122, 175, 308, 361, 1189, 2557, 2640, 2652, 2721, 2752, 2770, 3610, 3662, 4083, 4202], 'was': [123, 309, 536, 539, 763, 1239, 1253, 1271, 1377, 1426, 1454, 1505, 1550, 1557, 1623, 1651, 1665, 1735, 1744, 1785, 1807, 1953, 2070, 2096, 2127, 2298, 2327, 2655, 2821, 2827, 2835, 2870, 2890, 3676, 3713], 'observed': [125, 311, 2097, 2688, 2937, 4105], 'D111A/D113A.': [135, 321], 'Direct': [136, 322], 'measurement': [137, 323], 'bound': [140, 326, 2353], 'showed': [141, 327, 465, 864, 1103, 1883, 2120, 2303, 2405], '1–2': [145, 331], 'ions': [147, 333, 578, 983], 'each': [149, 335, 2355], 'molecule': [151, 337, 2357], 'due': [152, 338, 3523], 'mutations.': [155, 341], 'These': [156, 342, 641], 'results': [157, 343, 855, 1100, 1880, 2301, 3212, 3387, 4145], 'demonstrate': [158, 344], 'a': [159, 345, 812, 827, 868, 1007, 1177, 1222, 1408, 1654, 1714, 2240, 2434, 2524, 2555, 2617, 2681, 2704, 2760, 2798, 2968, 3230, 3254, 3320, 3344, 3443, 3482, 3608, 3632, 3660, 3810, 3975, 4149], 'role': [161, 347, 933, 3074, 3648, 4122, 4151], 'induce': [172, 358], 'required': [176, 362, 448, 598, 1146, 2308, 3311, 3382, 3406], 'supercoiled': [181, 367, 1356, 3969], 'enzyme.': [185, 371, 1337, 2880, 3665], 'is': [377, 447, 668, 944, 1001, 2239, 2899, 3323, 3519, 3800, 3933, 3938, 4045, 4112, 4139], 'best': [379], 'studied': [380, 1298], 'representative': [381], 'class': [389], 'includes': [392], 'bacterial': [394], 'archeal': [396], 'III,': [401, 409, 1796], 'reverse': [402], 'gyrase,': [403], 'yeast': [405, 941], 'mammalian': [407], 'diverse': [411], 'cellular': [414], 'functions': [415], '(reviewed': [416], 'Refs.': [418], '1.Wang': [419], 'J.C.': [420, 544, 655, 686, 722, 768, 914, 952, 1060, 1934, 3117, 3194, 3238, 3564, 4017], 'Annu.': [421], 'Rev.': [422], 'Biochem.': [423, 1608, 2167, 2607, 3292, 3921, 3949], '1996;': [424], '65:': [425], '635-692Crossref': [426], 'PubMed': [427, 441, 499, 518, 551, 591, 624, 638, 662, 699, 735, 779, 849, 906, 926, 963, 1052, 1072, 1168, 1322, 1612, 1701, 1926, 1946, 2014, 2031, 2156, 2378, 2584, 2611, 3049, 3068, 3109, 3129, 3186, 3206, 3245, 3428, 3556, 3576, 3744, 3848, 3878, 3906, 3956, 4026], 'Scopus': [428, 442, 500, 519, 552, 592, 625, 663, 700, 736, 780, 850, 907, 927, 964, 1053, 1073, 1169, 1613, 1702, 1927, 1947, 2015, 2032, 2157, 2171, 2379, 2585, 2612, 3050, 3069, 3110, 3130, 3187, 3207, 3246, 3296, 3429, 3557, 3577, 3745, 3879, 3907, 3957, 4027], '(2063)': [429], 'Google': [430, 444, 502, 521, 554, 594, 627, 639, 665, 702, 738, 782, 852, 909, 929, 966, 1055, 1075, 1171, 1323, 1615, 1704, 1929, 1949, 2017, 2034, 2159, 2173, 2381, 2587, 2614, 3052, 3071, 3112, 3132, 3189, 3209, 3248, 3298, 3431, 3559, 3579, 3747, 3849, 3881, 3909, 3928, 3959, 4029], 'Scholar': [431], '2.Tse-Dinh': [433], 'Y.-C.': [434, 487, 894, 1040, 1155, 1914, 2002, 2143, 2164, 2365, 2571, 3037, 3097, 3174, 3289, 3415, 3544, 3732, 3836, 3870, 3898, 3920, 3948, 4134], 'Biochim.': [435], 'Biophys.': [436, 3950], 'Acta.': [437], '1998;': [438, 491, 515, 696, 732, 846, 898, 918, 1044, 1064, 1918, 1938, 2006, 2028, 3041, 3065, 3101, 3121, 3178, 3198, 3548, 3568, 3736, 3953], '1400:': [439], '19-27Crossref': [440], '(51)': [443], 'Scholar).': [445, 522, 640, 703, 739, 783, 853, 930, 967, 1076, 1172, 1292, 1616, 1705, 1950, 2035, 2174, 2382, 2588, 3072, 3133, 3210, 3249, 3299, 3432, 3580, 3748, 3882, 3960, 4030], 'interconversion': [451], 'topological': [454], 'isomers': [455], 'catalyzed': [456], 'enzymes.': [459], 'Comparison': [460, 1727], 'their': [462, 1096, 1885, 2407, 2988], 'polypeptide': [463], 'that': [466, 556, 596, 709, 865, 1003, 1104, 1126, 1884, 2121, 2304, 2337, 2406, 2550, 2875, 3224, 3322, 3391, 3450, 3493, 3614, 3751, 3799, 3855, 4033, 4111], 'positions': [469], 'include': [470], '(3.Zhu': [478, 885, 1031, 1905, 1993, 3028, 3088, 3165, 3535, 3723], 'C.-X.': [479, 886, 1032, 1151, 1278, 1906, 1994, 2139, 2361, 2567, 3029, 3089, 3166, 3411, 3536, 3724, 3912], 'Roche': [480, 887, 1033, 1152, 1648, 1907, 1995, 2140, 2362, 2568, 3030, 3090, 3167, 3412, 3537, 3725], 'C.J.': [481, 888, 1034, 1153, 1908, 1996, 2141, 2363, 2569, 3031, 3091, 3168, 3413, 3538, 3726], 'Papanicolaou': [482, 889, 1035, 1909, 1997, 3032, 3092, 3169, 3539, 3727], 'N.': [483, 890, 1036, 1283, 1910, 1998, 3033, 3093, 3170, 3540, 3728], 'DiPietrantonio': [484, 891, 1037, 1911, 1999, 3034, 3094, 3171, 3541, 3729], 'A.': [485, 509, 546, 620, 657, 695, 731, 775, 892, 959, 1038, 1603, 1771, 1912, 2000, 2602, 3035, 3059, 3095, 3172, 3240, 3542, 3730, 3916, 3918, 3946, 4019], 'Tse-Dinh': [486, 893, 1039, 1154, 1279, 1913, 2001, 2142, 2163, 2364, 2570, 3036, 3096, 3173, 3288, 3414, 3543, 3731, 3869, 3897, 3919, 3947], 'J.': [488, 587, 633, 895, 915, 1041, 1061, 1156, 1317, 1607, 1915, 1935, 2003, 2144, 2165, 2366, 2572, 2606, 3038, 3098, 3118, 3175, 3195, 3290, 3416, 3545, 3565, 3733, 3839, 4020], 'Biol.': [489, 896, 916, 1042, 1062, 1157, 1916, 1936, 2004, 2145, 2367, 2573, 3039, 3099, 3119, 3176, 3196, 3417, 3546, 3566, 3734, 3840, 3923, 4022], 'Chem.': [490, 897, 917, 1043, 1063, 1158, 1917, 1937, 2005, 2146, 2368, 2574, 3040, 3100, 3120, 3177, 3197, 3418, 3547, 3567, 3735, 3841], '273:': [492, 899, 919, 1045, 1065, 1919, 1939, 2007, 3042, 3102, 3122, 3179, 3199, 3549, 3569, 3737], '8783-8789Abstract': [493, 900, 1046, 1920, 2008, 3043, 3103, 3180, 3550, 3738], 'Full': [494, 496, 901, 903, 921, 923, 1047, 1049, 1067, 1069, 1163, 1165, 1921, 1923, 1941, 1943, 2009, 2011, 2151, 2153, 2373, 2375, 2579, 2581, 3044, 3046, 3104, 3106, 3124, 3126, 3181, 3183, 3201, 3203, 3423, 3425, 3551, 3553, 3571, 3573, 3739, 3741, 3845], 'Text': [495, 497, 902, 904, 922, 924, 1048, 1050, 1068, 1070, 1164, 1166, 1922, 1924, 1942, 1944, 2010, 2012, 2152, 2154, 2374, 2376, 2580, 2582, 3045, 3047, 3105, 3107, 3125, 3127, 3182, 3184, 3202, 3204, 3424, 3426, 3552, 3554, 3572, 3574, 3740, 3742, 3846], 'PDF': [498, 905, 925, 1051, 1071, 1167, 1925, 1945, 2013, 2155, 2377, 2583, 3048, 3108, 3128, 3185, 3205, 3427, 3555, 3575, 3743, 3847], '(39)': [501, 908, 1054, 1928, 2016, 3051, 3111, 3188, 3558, 3746], 'Scholar,': [503, 628, 910, 1056, 1930, 2018, 2160, 3053, 3113, 3190, 3560, 3910], '4.Suerbaum': [504, 3054], 'S.': [505, 619, 694, 730, 757, 774, 958, 1605, 2604, 3055], 'Brauer-Steppkes': [506, 3056], 'T.': [507, 1601, 2600, 3057], 'Labigne': [508, 3058], 'Cameron': [510, 3060], 'B.': [511, 3061], 'Drlica': [512, 1315, 3062], 'K.': [513, 1316, 3063], 'Gene.': [514, 3064], '210:': [516, 3066], '151-161Crossref': [517, 3067], '(29)': [520, 3070], 'When': [523, 2997], 'crystal': [525], 'structure': [526, 651, 680, 1776], '67-kDa': [529, 650, 3998, 4054], 'N-terminal': [530], 'transesterification': [531, 3999, 4055, 4088], 'domain': [532, 646, 673, 814, 4000, 4056, 4089, 4092, 4126], 'published,': [537], 'it': [538, 3937], 'noted': [540], '(5.Lima': [541, 652, 3235], 'C.D.': [542, 653, 3236, 4015], 'Wang': [543, 654, 685, 721, 767, 913, 951, 1059, 1933, 3116, 3193, 3237, 3563, 4016, 4221], 'Mondragón': [545, 656, 3239, 4018], 'Nature.': [547, 658, 1697, 3241], '1994;': [548, 659, 3242], '367:': [549, 660, 3243], '138-146Crossref': [550, 661, 3244], '(266)': [553, 664, 3247], 'Scholar)': [555, 595, 1324, 2615], 'three': [558, 570, 873, 970, 1131, 1489, 1554, 3830], 'arranged': [566], 'similarly': [567], 'known': [573], 'coordinate': [575], 'divalent': [577, 982, 3231], 'Klenow': [580], 'fragment': [581, 2801, 2929, 2945, 3634, 3854, 3886], '(6.Beese': [582], 'L.S.': [583, 609], 'Steitz': [584, 612, 631], 'T.A.': [585, 613, 632], 'EMBO': [586], '1991;': [588, 1609, 2168, 2608, 3293], '10:': [589], '25-33Crossref': [590], '(916)': [593], 'nucleotidyl': [601, 831], 'transfer': [602], '(7.Freemont': [604], 'P.S.': [605], 'Friedman': [606], 'J.M.': [607], 'Beese': [608], 'Sanderson': [610], 'M.R.': [611], 'Proc.': [614, 689, 725, 769, 953], 'Natl.': [615, 690, 726, 770, 954], 'Acad.': [616, 691, 727, 771, 955], 'Sci.': [617, 692, 728, 772, 956], 'U.': [618, 693, 729, 773, 957], '1988;': [621, 3842], '85:': [622], '8924-8928Crossref': [623], '(326)': [626], '8.Joyce': [629], 'C.M.': [630], 'Bacteriol.': [634, 1318], '1995;': [635, 3925], '177:': [636], '6321-6329Crossref': [637], 'Scholar),': [666, 3850, 3929], 'which': [667, 2423], 'similar': [669, 1329, 2632, 3594], 'B′': [672], 'theSaccharomyces': [675], 'cerevisiae': [676, 758], 'II': [679, 943, 2982], '(9.Berger': [681, 717], 'J.M': [682, 718], 'Fass': [683, 719], 'D.': [684, 720], 'Harrison': [687, 723], 'S.C.': [688, 724], '95:': [697, 733], '7876-7881Crossref': [698, 734], '(89)': [701, 737], 'There': [704, 2238], 'corresponding': [706, 3010], 'topoisomerases': [716, 2984], 'Severe': [740], 'cleavage': [746, 3811, 3861, 4041, 4099], 'activities': [747, 836, 1887, 1899, 2418], 'when': [749, 1895, 2824, 2838, 3936], 'one': [750, 870, 1141, 2044, 2230, 3137, 3463, 3695], 'triad': [754, 1855, 2048, 2095, 2234, 2274, 2388, 3141, 3440, 4155], 'II,': [761], 'Asp-530,': [762], 'mutated': [764], '(10.Liu': [765, 949], 'Q': [766, 950], '1999;': [776, 960], '96:': [777, 961], '881-886Crossref': [778, 962], '(65)': [781, 965], 'Another': [784], 'glutamate': [786], 'at': [787, 800, 1139, 1378, 1459, 1482, 1512, 1528, 1559, 1653, 1668, 1773, 1778, 1981, 2041, 2054, 2098, 2187, 2227, 2253, 2275, 2288, 2330, 2662, 2674, 2707, 2730, 3283, 3304, 3337, 3379, 3446, 3473, 3672, 3694, 3716, 3719, 3774, 3865, 4002, 4043, 4073, 4101], 'Glu-9': [788, 1982, 2042, 2228, 3076, 3461, 3529], 'E.': [790, 1303, 2476, 2948, 3018, 3262], 'aspartates': [797], 'motif': [798, 977, 4166], 'DXD': [799, 976, 4165], 'Asp-111': [801, 3160, 3673, 3720, 3752, 4168], 'Asp-113': [803, 3675, 3722, 3754, 4170], 'proposed': [806, 3087], 'be': [808, 995, 1017, 2179, 2200, 2687, 2896, 3026, 3351, 3369, 3522, 3857, 4071, 4204], 'motifs': [810, 3834, 3944, 3963], 'catalytic': [813, 938, 2995], 'named': [815], 'Toprim': [816], 'topoisomerases,': [823], 'as': [824, 826, 1275, 1597, 2122, 2124, 2507, 2532, 2596, 2786, 2788, 3993], 'well': [825, 3350], 'number': [828], 'other': [830, 4193], 'transferases': [832], 'polynucleotide': [834], 'cleaving': [835], '(11.Aravind': [837], 'L.': [838, 2020], 'Leipe': [839, 2021], 'D.D.': [840, 2022], 'Koonin': [841, 2023], 'E.V.': [842, 2024], 'Nucleic': [843, 2025], 'Acids': [844, 2026], 'Res.': [845, 2027, 3951], '26:': [847, 2029], '4205-4213Crossref': [848, 2030], '(306)': [851, 2033], 'However,': [854, 2680, 3134], 'site-directed': [857, 1248], 'mutagenesis': [858, 1249], 'inE.': [859, 1190, 1804], 'conversion': [866, 3135], 'single': [869, 1008, 1903, 3345, 3707], 'alanine': [878, 1801, 1862, 1979, 2039, 2082, 2225, 3147, 3302, 3602, 3670, 3692, 3708], 'did': [879, 2424, 2716, 3604, 3625], 'abolish': [881], '12.Chen': [911, 1057, 1931, 3114, 3191, 3561], 'S.-J.': [912, 1058, 1932, 3115, 3192, 3562], '6050-6056Abstract': [920, 1066, 1940, 3123, 3200, 3570], '(57)': [928, 1074, 1948, 3131, 3208, 3578], 'Asp-530': [935], 'mechanism': [939], 'also': [945, 1175, 2758, 3777], 'entirely': [947], 'clear': [948], 'Whether': [968], 'participate': [978], 'coordination': [980, 3347, 3366], 'enzyme-DNA': [986], 'complex': [987], 'during': [988, 3233], 'removal': [989], 'negative': [991], 'supercoils': [992], 'remained': [993, 2260], 'established': [996, 4148], 'biochemical': [998], 'analysis.': [999], 'It': [1000], 'possible': [1002], 'coordinating': [1010, 1138, 4068], 'residue': [1011, 2912, 4109], 'can': [1016, 2199, 3856, 4006, 4070], 'tolerated': [1018, 3353], 'under': [1022, 1891, 2429, 2509, 2534, 2959, 2972], 'reaction': [1023, 2297, 2326, 4130], 'conditions': [1025, 2431, 2505, 2530], '>2': [1027], 'present': [1030, 1558], 'Double': [1077, 2036, 3458], 'lacking': [1081], 'now': [1090], 'purified': [1092, 1240, 1274, 1326, 1828, 1846], 'analysis': [1094, 1511, 2398, 4119], 'enzymatic': [1097], 'activities.': [1098], 'presented': [1101, 4146], 'here': [1102, 1299, 3214, 3389, 3591, 4147], 'involving': [1110, 2092, 2224, 2271, 3460, 3511, 4084], 'requires': [1115], 'higher': [1116, 2710], 'activity,': [1122, 2466, 3155], 'supporting': [1123], 'hypothesis': [1125, 3223], 'carboxylates': [1128], 'involved': [1136, 4173], 'least': [1140, 3163], '(13.Zhu': [1150, 2138, 2360, 2566, 3410], '1997;': [1159, 2147, 2369, 2575, 3419], '272': [1160, 2148, 2370, 2576, 3420], '(12621):': [1161, 2149, 2371, 2577, 3421], '16206Abstract': [1162, 2150, 2372, 2578, 3422], '(44)': [1170, 2158, 2172, 2380, 2586, 3297, 3430], 'We': [1173, 2333, 2546, 3981, 4031, 4216], 'developed': [1176, 2759], 'digestion': [1179, 1733, 1756, 1759, 2765, 2809, 2888, 2909, 2923, 2942, 2953, 3583, 3638, 3687, 3797], 'using': [1181, 1738, 2763], 'endoproteinase': [1183, 1646, 1762], 'detect': [1185, 2767], 'Mg(II)-induced': [1187, 4200], 'I.': [1194], 'chemical': [1196], 'reagents': [1197], 'used': [1198, 1254, 1332, 1745], 'either': [1200, 1713], 'ultrapure': [1201], 'ACS': [1203], 'reagent': [1204], 'grade.': [1205], 'Solutions': [1206], 'prepared': [1208], 'water': [1210], 'first': [1211], 'deionized': [1212], 'Barnstead': [1215], 'Nanopure': [1216], 'system': [1217], 'then': [1219, 1468], 'passed': [1220], 'over': [1221, 1433], 'Bio-Rad': [1223, 1498], 'chelex': [1224], '100': [1225], 'resin': [1226], '(100–200': [1227], 'mesh': [1228], 'sodium': [1229], 'form)': [1230], 'remove': [1232], 'any': [1233, 2427], 'contaminating': [1234], 'metal': [1235, 3280], 'ions.': [1236], 'Plasmid': [1237], 'cesium': [1242], 'chloride': [1243], 'gradient': [1244, 1718], 'centrifugation.': [1245], 'QuikChange': [1247], 'kit': [1250], 'from': [1251, 2876, 2911, 3270, 3785, 3817, 3985, 4108], 'Stratagene': [1252], 'construction': [1256], 'mutants.': [1259, 2084], 'identified': [1263], 'sequencing.': [1266], 'Wild': [1267, 1338, 1617], 'expressed': [1272, 1301], 'described': [1276, 1598, 2508, 2533, 2597, 3213], '(14.Zhu': [1277], 'Bjornsti': [1280], 'M.-A.': [1281], 'Osheroff': [1282], 'Topoisomerase': [1285], 'Protocols.': [1286], 'Humana': [1287], 'Press,': [1288], 'Totowa,': [1289], 'NJ1999:': [1290], '145-151Google': [1291], 'GP200': [1305, 1806], '(gyrA(Nalr)gyrB225Δ(topAcysB)204)': [1306], '(15.Pruss': [1307], 'G.J.': [1308], 'Franco': [1309], 'R.J.': [1310], 'Chevalier': [1311], 'S.G.': [1312], 'Manes': [1313], 'S.H.': [1314], '1986;': [1319], '168:': [1320], '276-282Crossref': [1321], 'procedures': [1328], 'those': [1331], 'assayed': [1344, 1868], '20': [1349, 1471, 1563, 1626, 2188, 2677, 2731], 'μl': [1350, 1393], '0.5': [1352, 2789], 'μg': [1353, 1661], 'negatively': [1355], 'plasmid': [1357], 'DNA,': [1358], '10': [1359, 1537, 1660, 2331, 3273], 'Tris-HCl,': [1361], 'pH': [1362, 1419, 1475, 1567, 1630], '8.0,': [1363], '50': [1364, 1397], 'NaCl,': [1366], '0.1': [1367, 1569, 1632], 'mg/ml': [1368], 'gelatin,': [1369], 'indicated': [1372, 1639, 1673], 'concentration': [1373, 1504, 1640, 2065, 2109, 2209, 2279, 2826, 3267, 3479], 'MgCl2.': [1375, 2256], 'Incubation': [1376, 2527], '37': [1379, 1669], '°C': [1380, 1484, 1670], '30': [1382, 2305], 'min.': [1383, 2332], 'reactions': [1385], 'stopped': [1387, 1678], 'addition': [1390, 1681], '5': [1392, 1535, 2734], '50%': [1395], 'glycerol,': [1396], 'EDTA,': [1399], '0.5%': [1401], '(v/v)': [1402], 'bromphenol': [1403], 'blue.': [1404], 'After': [1405], 'electrophoresis': [1406, 1711, 1812], '0.7%': [1409], 'agarose': [1410, 1842], 'gel': [1411, 1687, 1694, 1720, 1811], 'TAE': [1413], 'buffer': [1414, 1490, 1582, 1689], '(40': [1415], 'Tris': [1417], 'acetate,': [1418], '8.1,': [1420], '2': [1421, 1457, 2347, 2350, 2484, 2628, 2664, 2830, 2852], 'EDTA),': [1423], 'stained': [1427], 'ethidium': [1429], 'bromide': [1430], 'photographed': [1432], 'UV': [1434], 'light.': [1435], 'To': [1436, 1585, 2262], 'measure': [1437], 'stoichiometry': [1440, 2437], 'Mg(II),': [1442, 2291, 2666, 2699, 4038, 4080], '2.5': [1443, 3284], 'ml': [1444], '(1': [1452], 'mg/ml)': [1453], 'incubated': [1455, 2312], 'mmMgCl2': [1458, 2100, 2732], 'room': [1460, 1529], 'temperature': [1461], '(∼25': [1462], '°C)': [1463], '1': [1465, 1560, 2451], 'h,': [1466], 'dialyzed': [1469, 1624], 'potassium': [1473, 1565, 1628], 'phosphate,': [1474, 1566, 1629], '7.4,': [1476, 1568], '0.1m': [1477], 'KCl,': [1478, 1634], '0.2': [1479, 1635], 'dithiothreitol': [1481], '4': [1483], '24': [1486], 'h': [1487], 'changes.': [1491], 'Protein': [1492], 'determined': [1495, 1506, 2516, 2541, 2891, 2963, 2976], 'Dc': [1499], 'protein': [1500, 1775, 3827, 4081], 'reagent.': [1502], 'Magnesium': [1503], 'inductively': [1508, 2395], 'coupled': [1509, 2396], 'plasma': [1510, 2397], 'Quantitative': [1513], 'Technologies': [1514], 'Inc.': [1515], '(Whitehouse,': [1516], 'NJ).': [1517], 'Fluorescence': [1518], 'measurements': [1519, 1574], 'performed': [1521, 1767, 1786], 'Perkin-Elmer': [1524], 'LS-5B': [1525], 'luminescence': [1526], 'spectrometer': [1527], 'temperature.': [1530], 'spectral': [1532], 'bandwidths': [1533], 'nm,': [1538], 'respectively': [1539], 'excitation': [1541], '(295': [1542], 'nm)': [1543], 'emission.': [1545], 'Each': [1546], 'data': [1547, 1594, 2593], 'point': [1548, 3321], 'reported': [1549, 1900], 'average': [1552, 2513, 2538], 'determinations.': [1555], 'Enzyme': [1556], 'μm': [1561], 'm': [1570, 1633], 'KCl.': [1571], 'All': [1572], 'corrected': [1576], 'spectrum': [1579], 'solution': [1583], 'used.': [1584], 'calculate': [1586], 'dissociation': [1588, 2618], 'constant': [1589, 2619], 'binding,': [1592, 3761], 'analyzed': [1596, 1709], 'previously': [1599, 2335, 2548, 2598], '(16.Bhattacharyya': [1600, 2599], 'Bhattacharyya': [1602, 2601], 'Roy': [1604, 2603], 'Eur.': [1606, 2605], '200:': [1610, 2609], '739-745Crossref': [1611, 2610], '(34)': [1614, 2613], 'into': [1625], '7.5,': [1631], 'mmdithiothreitol': [1636], 'MgCl2present.': [1642], 'sequencing': [1644], 'grade': [1645], '(from': [1647], 'Molecular': [1649], 'Biochemicals)': [1650], 'added': [1652], 'ratio': [1655], '1:50': [1657], '(w/w)': [1658], 'topoisomerase.': [1663], 'Digestion': [1664], 'carried': [1666, 1736], 'out': [1667, 1737], 'length': [1674], 'time': [1676, 2292, 2806], 'equal': [1683], 'volume': [1684], '2×': [1686], 'loading': [1688], 'Laemmli': [1692], 'SDS': [1693, 1810], '(17.Laemmli': [1695], 'UK': [1696], '1970;': [1698], '227:': [1699], '680-685Crossref': [1700], '(206631)': [1703], 'samples': [1707], '15': [1715, 2099, 2254, 2281], '5–20%': [1717], 'SDS-polyacrylamide': [1719], 'followed': [1721, 1817, 2393], 'staining': [1723, 1821], 'Coomassie': [1725, 1819], 'Blue.': [1726], 'intensities': [1729], '14-kDa': [1732, 1754, 2799, 2819, 2833, 2867, 2886, 3633, 3795, 3853, 3884, 4106], 'product': [1734, 2820, 2834, 2868, 2889, 2910, 3798, 4107], 'AlphaImager': [1740], 'software.': [1741], 'Mass': [1742, 1783], 'spectroscopy': [1743, 1784, 2894], 'determine': [1747], 'molecular': [1750], 'mass': [1751, 1764, 1793, 2893, 2904, 2957], 'product.': [1757], 'In-gel': [1758], 'Lys-C': [1761, 2922, 2941], 'mapping': [1765], 'Dr.': [1769, 4218], 'V.': [1770], 'Fried': [1772], 'facility': [1777], 'New': [1779], 'York': [1780], 'Medical': [1781], 'College.': [1782], 'matrix-assisted': [1788], 'laser': [1789], 'desorption': [1790], 'ionization': [1791], 'time-of-flight': [1792], 'spectrometry': [1794], '(Kompact': [1795], 'Kratos).': [1797], 'Expression': [1798], 'substitution': [1802, 1980, 2083, 2226, 3709], 'confirmed': [1808, 2932], 'soluble': [1815], 'lysates': [1816], 'Blue': [1820], '(data': [1822], 'shown).': [1824], '>95%': [1830], 'homogeneity': [1831], '(Fig.1)': [1832], 'combination': [1835], 'phosphocellulose,': [1837], 'hydroxyapatite,': [1838], 'single-stranded': [1840], 'column': [1843], 'chromatography.': [1844], 'substitutions': [1863, 2040, 3303, 3603, 3671, 3693], 'diluted': [1865], 'serially': [1866], 'presence': [1874, 2784, 2850, 3333, 3805, 4078], 'Mg(II).': [1878, 2629, 2679, 2777, 2814, 3476, 3599], '(Fig.': [1881, 2058, 2101, 2236, 2649, 2733, 2855], '2)': [1882], 'further': [1889, 2263, 2669, 2822, 4115], 'diminished': [1890], 'this': [1892, 2747, 2818, 2926, 2933, 3983, 4142, 4199], 'condition': [1894], 'compared': [1896, 2071], 'No': [1951], 'detected': [1954], 'D111A/D113A': [1957, 2204, 2840, 3641], 'mutant.': [1964, 2205, 2748], 'D111A/E115A': [1966, 2443, 2693, 2859, 3395], 'D113A/E115A': [1968, 2445, 2695, 2861, 3397], '<10%': [1972], 'has': [1983, 3085, 3887, 4010], 'shown': [1985, 2336, 2519, 2544, 2549, 2779, 3253, 3388], '11.Aravind': [2019], 'MgCl2': [2057, 2111, 2486, 2635], '2).': [2059], 'effect': [2061, 2215, 3164, 3359, 3484, 3526, 3667, 3704], 'increasing': [2063], 'on': [2066, 2216, 3485, 3710, 3892, 4188], 'between': [2072, 2696, 3257, 4052], 'Maximal': [2085, 2651], '3).': [2102, 2237], 'With': [2103, 3300], 'enzyme,': [2106, 3356, 3437, 4190], 'such': [2107], 'high': [2108, 2277, 3976], 'inhibition': [2114, 3454], 'Previous': [2118, 3250], 'studies': [2119, 3251], 'little': [2123, 2787], '1.5–2.5': [2125], 'sufficient': [2128], '18.Domanico': [2161], 'P.L.': [2162, 3287], 'Inorg.': [2166, 3291], '24:': [2169, 3294], '87-96Crossref': [2170, 3295], 'Relaxation': [2175], 'could': [2177, 2686, 3451], 'restored': [2180], 'even': [2186, 2729, 3494], 'MgCl2,': [2190], 'only': [2192, 3148, 3481], 'partial': [2193, 3151], 'input': [2197], 'achieved': [2201, 2656, 3282], 'increased': [2207, 2828], 'much': [2211, 2638, 3370], 'less': [2212], 'slight': [2241, 3483], 'enhancement': [2242], 'E9A/D111A': [2249], 'E9A/D113A': [2251], 'E9A/E115A': [2258], 'inactive.': [2261], 'compare': [2264], 'versus': [2283], 'course': [2293, 2807], 'monitored.': [2299], '(Fig.4)': [2302], 'min': [2306], 'approach': [2318], 'relaxation,': [2320], 'whereas': [2321, 2456, 3357], 'nearly': [2328], 'complete': [2329], 'following': [2338], 'incubation': [2339, 2482], 'mmMgCl2,': [2348], 'around': [2349, 2450, 2621, 2663], 'remains': [2352], 'after': [2358, 2481, 3813], 'dialysis': [2359, 2488, 2504, 2529], 'Similar': [2383], 'treatment': [2384], 'content': [2402, 2474], '(Table': [2403, 2930], 'I)': [2404], 'stoichiometries': [2410], 'reduced,': [2412], 'correlation': [2414], 'observed.': [2419], 'mutant,': [2422], 'show': [2426], 'all': [2430, 3586], 'tested,': [2432], 'barely': [2438], 'above': [2439], 'background.': [2441], 'retained': [2447], 'per': [2453], 'molecule,': [2455], 'D111A/D113A,': [2460], 'severely': [2464], 'reduced': [2465], 'significantly': [2468, 3317], 'lower': [2469, 2639, 2873, 3496], 'stoichiometry.Table': [2472], 'IMagnesium': [2473], 'treatmentEnzymeMagnesium': [2489], 'contentatom/molecule': [2490], 'enzymeWild': [2491], 'type2.32': [2492], '±': [2493, 2495, 2497, 2499, 2501], '0.03D111A/D113A0.22': [2494], '0.02D111A/E115A1.11': [2496], '0.01D113A/E115A1.08': [2498], '0.01D111A/D113A/E115A0.01': [2500], '0.01Incubation': [2502], '"Experimental': [2510, 2535], 'Procedures."': [2511, 2536], 'values': [2517, 2542], 'here.': [2520, 2545], 'Open': [2521, 2965], 'table': [2522, 2966], 'new': [2525, 2969], 'tab': [2526, 2970], 'result': [2553, 2718], 'decreased': [2563, 3504], 'tryptophan': [2564, 2642, 2754], 'fluorescence': [2565, 2592, 2643, 2654, 2673, 2685, 2723], 'Analysis': [2589], '(Fig.5': [2594], 'A)': [2595], 'yielded': [2616], '0.3': [2622], 'Titration': [2630, 2713], 'emission': [2644, 2724], '5).': [2650], 'significant': [2670, 2720], 'drop': [2671], 'up': [2675], 'second': [2682, 2705, 3404], 'decrease': [2683], '10–15': [2697], 'suggesting': [2700], 'concentrations.': [2712], 'B),': [2735], 'agreement': [2737], 'abolishment': [2739], 'Besides': [2749, 4184], 'monitoring': [2750], 'fluorescence,': [2755], 'we': [2756], 'upon': [2774], 'As': [2778], 'Fig.': [2781], '6,': [2782], 'accumulation': [2796], 'seen': [2803, 2837, 3506], 'absence': [2812, 3597, 4036], 'yield': [2816], 'enhanced': [2823, 3935], 'mm.': [2831], 'digested': [2845], '7).': [2856], 'For': [2857], 'mutants,': [2862], 'level': [2864], 'formed': [2869, 3802, 3858], 'about': [2871], '3-fold': [2872], 'than': [2874, 3689, 3718], 'weight': [2883], '14,498.': [2897], 'almost': [2900], 'identical': [2901], 'predicted': [2905], '736': [2913], '862': [2915], '(14,509.5).': [2916], 'masses': [2918, 2938], 'in-gel': [2921, 2940], 'products': [2924, 2943], '14': [2927], 'kDa': [2928], 'II)': [2931], 'identification.Table': [2934], 'IIPredicted': [2935], '736–862': [2946, 4110], 'ILys-C': [2952], 'productPredicted': [2954], 'massObserved': [2955], 'massatomic': [2956], 'units736–737250.3ND738–741518.6ND742–7521194.41195.2753–7651466.71466.9766–7882431.82430.5789–8102762.22763.1811–8261816.01814.7827–8341025.31025.3835–836248.3ND837–844969.0970.0845–847319.3ND848–8591302.41301.1860–862433.5NDMasses': [2958], '900': [2960, 2973], '(ND).': [2964, 2977], 'Masses': [2971], 'Type': [2978], 'share': [2985], 'similarity': [2986], 'requirement': [2989, 3281], 'mechanism.': [2996], 'classes': [3003], 'compared,': [3007], 'Glu-9,': [3012, 3512], 'A': [3073], 'breaking': [3079], 'rejoining': [3081], 'strand': [3084], 'mutation': [3158, 3530], 'having': [3161], 'provided': [3219], 'support': [3220], 'bind': [3229, 3442], 'ion': [3232], 'positive': [3255], 'relationship': [3256], 'colitopoisomerase': [3263], '0': [3271], 'mm,': [3274], 'saturation': [3277], '(18.Domanico': [3286], 'triad,': [3307], 'higher,': [3318], 'In': [3331, 3433, 3701, 4076], 'phosphates': [3336], 'site,': [3340], 'sites': [3348, 3367], 'may': [3349, 3441, 3500, 3615, 3755, 3776], 'easily': [3352], 'would': [3368, 3768, 4203], 'severe': [3372, 3609, 3678, 3715], 'affinity': [3376, 3499, 3932, 3977], 'position': [3381, 4074], 'suggest': [3390], 'mutations': [3394], 'primarily': [3398], 'affect': [3399], 'third': [3444], '15–20': [3447], 'lead': [3452, 3606, 3627], 'triads': [3467, 3652], 'Increased': [3477], 'supports': [3490, 3646], 'interpretation': [3492], 'though': [3495], 'contribute': [3501], 'major': [3514], 'reason': [3515], 'deficiency': [3518], 'likely': [3520], 'related': [3531], 'cleavage/religation': [3534], 'patterns': [3584], 'examined': [3590], 'quite': [3593], 'Therefore,': [3600], 'folding': [3613], 'account': [3616], 'Addition': [3622], 'appearance': [3630], 'resulting': [3658, 3791, 4180], 'both': [3680, 3765], 'Glu-115.': [3700], 'contrast,': [3702], 'indicates': [3750], 'overlapping': [3757], 'but': [3762, 3930, 4009], 'elimination': [3763], 'groups': [3767], 'greatly': [3769, 3934], 'diminish': [3770], 'binding.': [3772], 'Mutation': [3773], 'influence': [3778], 'another': [3779, 3852], 'aspect': [3780], 'function,': [3783], 'aside': [3784], 'change.': [3793, 4183], 'preferentially': [3801], 'corresponds': [3808], 'Glu-735.': [3814], 'region': [3816, 3984], 'amino': [3818, 3986, 4003, 4194], 'acid': [3819, 3987, 4004, 4195], '598': [3820, 3988], 'C': [3823, 3991], 'terminus': [3824, 3992], 'contains': [3828], 'Zn(II)': [3831, 3942, 3962, 4059, 4067], 'tetracysteine': [3833], '(19.Tse-Dinh': [3835], 'Beran-Steed': [3837], 'R.K.': [3838, 3868, 3896], '263:': [3843], '15857-15859Abstract': [3844], 'tryptic': [3860, 3885], 'Arg-744': [3866], '(20.Beran-Steed': [3867, 3895], 'Proteins': [3871, 3899], 'Struct.': [3872, 3900], 'Funct.': [3873, 3901], 'Genet.': [3874, 3902], '1989;': [3875, 3903], '6:': [3876, 3904], '249-258Crossref': [3877, 3905], '(46)': [3880, 3908], 'single-strand': [3888], 'its': [3893], 'own': [3894], '21.Zhu': [3911], 'Samuel': [3913], 'M.': [3914], 'Pound': [3915], 'Ahumada': [3917, 4132], 'Mol.': [3922, 4021], 'Intern.': [3924], '35:': [3926], '375-385PubMed': [3927], 'linked': [3939], '(22.Ahumada': [3945], 'Commun.': [3952], '251:': [3954], '509-514Crossref': [3955], '(23)': [3958], 'thus': [3972], 'part': [3973], 'domain.': [3980, 3996], 'denote': [3982], 'ZD': [3995, 4091, 4125], 'terminating': [4001], '597': [4005], 'cleave': [4007], '(23.Lima': [4014], '1993;': [4023], '232:': [4024], '1213-1216Crossref': [4025], '(43)': [4028], 'postulate': [4032], '735': [4044], 'accessible': [4047], 'because': [4048], 'protein-protein': [4050], 'interactions': [4051], 'motifs.': [4061], 'last': [4063], '12': [4066], 'cysteines': [4069], '736.': [4075], 'separation': [4085], 'takes': [4093], 'place': [4094], 'expose': [4096], 'Glu-735,': [4102], 'forming': [4103], 'resistant': [4113], 'Biochemical': [4118], '1A.': [4131], 'Tse-Dinh,': [4135], 'manuscript': [4136], 'preparation.': [4138], 'consistent': [4140], 'interpretation.': [4143], 'additional': [4185], 'structural': [4186], 'information': [4187], 'identification': [4191], 'helpful': [4205], 'elucidation': [4207], 'dynamic': [4210], 'action': [4211], 'thank': [4217], 'James': [4219], 'C.': [4220], 'communication': [4223], 'discussions': [4225], 'results.': [4227]}, 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