Publication Information

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385, 400, 479, 504, 514, 609, 616, 655, 675, 753, 759, 772, 816, 828, 897, 913, 961, 975, 982, 986, 1368, 1541, 1567, 1582, 1740, 1857, 1908, 1917, 1932, 1949, 1969, 1977, 1989, 2000, 2014, 2035, 2066, 2187, 2230, 2270, 2345, 2356, 2372, 2418, 2457, 2466, 2492, 2553, 2561, 2611, 2756, 2779, 2787, 2792, 2865, 2873, 2881, 2888, 2906, 2925, 2945, 2961, 2971, 2989, 3009, 3034, 3127, 3136, 3167, 3239, 3285, 3300, 3312, 3726, 3742, 3755], 'protozoan': [8, 199, 383], 'parasite': [9, 200, 3803], 'Toxoplasma': [10, 201, 388, 1378, 2001], 'gondii': [11, 53, 105, 134, 202, 244, 296, 325, 389, 1401, 1811, 1934, 1979, 2078, 2262, 2798, 3021, 3130, 3155, 3287, 3314, 3335, 3758, 3782], 'and': [12, 57, 61, 173, 180, 203, 248, 252, 364, 371, 390, 416, 501, 613, 682, 745, 757, 819, 978, 991, 1006, 1414, 1736, 1847, 1924, 1936, 1942, 1961, 1986, 2016, 2038, 2056, 2118, 2150, 2191, 2268, 2379, 2487, 2551, 2616, 2658, 2676, 2721, 2732, 2737, 2754, 2916, 2932, 2939, 2948, 2981, 3012, 3141, 3159, 3190, 3211, 3252, 3315, 3377, 3397, 3426, 3766, 3784, 3802, 3869, 4160], 'its': [13, 204, 962, 1937], 'similarity': [14, 205], 'to': [15, 18, 43, 90, 140, 144, 206, 209, 234, 281, 331, 335, 493, 611, 618, 689, 769, 776, 831, 840, 1002, 1311, 1325, 1329, 1390, 1396, 1551, 1852, 1890, 1912, 1925, 1957, 2044, 2099, 2183, 2214, 2359, 2479, 2628, 2884, 2901, 2991, 3019, 3079, 3147, 3170, 3235, 3325, 3333, 3402, 3420, 3764, 3867, 3906], 'Plasmodium': [16, 207, 391, 1576, 1585, 1865], 'falciparum': [17, 75, 208, 266, 1804, 3731, 3769, 3877], 'investigate': [19, 210, 3739], 'influence': [21, 212], 'specific': [23, 214, 1007, 3427], 'dihydrofolate': [24, 215, 627, 635, 645], 'reductase': [25, 216, 628], 'polymorphisms': [26, 217, 1544, 1800, 3728, 3814], 'known': [27, 218, 4064], 'from': [28, 219, 497, 510, 774, 1308, 1393, 2115, 2795, 2896, 3197, 4068], 'field': [29, 220], 'isolates': [30, 221], 'drug-resistant': [32, 223, 1384, 1546, 1922, 3767], 'malaria.': [33, 190, 224, 381], 'By': [34, 225, 959, 1944], 'engineering': [35, 226, 1945], 'appropriate': [36, 227], 'recombinant': [37, 228, 1950, 2036, 2271, 2667], 'shuttle': [38, 229, 1951], 'vectors,': [39, 230, 1952], 'it': [40, 231, 1404, 1876, 1953], 'is': [41, 162, 232, 353, 605, 767, 2018, 2876, 3414, 3733], 'feasible': [42, 233, 1956], 'examine': [44, 235, 1853, 1958], 'mutations': [45, 117, 179, 236, 308, 370, 1009, 1319, 1385, 1920, 1971, 2420], 'by': [46, 92, 125, 159, 237, 283, 316, 350, 624, 1373, 2020, 2196, 2568, 2729, 2743, 2750, 2763, 2968, 3157, 3241, 3347, 3385, 4158], 'transient': [47, 238, 1973], 'or': [48, 239, 1884, 1974, 2226], 'stable': [49, 240, 1569, 1975], 'transformation': [50, 241, 1742, 1976, 2040, 3804], 'T.': [52, 85, 243, 276, 712, 1184, 1400, 1664, 1714, 1810, 1933, 1978, 2077, 2261, 2348, 2797, 3129, 3286, 3313, 3334, 3395, 3606, 3757, 3825, 3919, 4018, 4206], 'parasites,': [54, 245, 1980], 'in': [55, 84, 96, 110, 113, 189, 246, 275, 287, 301, 304, 380, 419, 482, 582, 602, 658, 665, 680, 750, 845, 900, 908, 989, 1010, 1377, 1386, 1419, 1545, 1560, 1587, 1802, 1808, 1860, 1921, 1939, 1959, 1962, 2026, 2031, 2071, 2155, 2164, 2208, 2223, 2228, 2235, 2259, 2266, 2369, 2424, 2472, 2497, 2500, 2558, 2620, 2670, 2735, 2774, 2843, 2848, 3217, 3424, 3431, 3735, 3815, 4006, 4149, 4154], 'bacterial': [56, 247, 1570, 1981, 2039, 2073, 3779, 3800], 'yeast': [58, 249], 'complementation': [59, 250, 1984, 2343, 3801], 'assays,': [60, 251, 1985], 'through': [62, 253], 'biochemical': [63, 254, 1930, 1987, 4161], 'analysis': [64, 175, 255, 366, 1988, 2344], 'purified': [66, 257, 1990, 2712, 2738], 'enzyme.': [67, 258, 1991], 'A': [68, 259, 598, 994, 2059, 2103, 3724], 'series': [69, 260, 3754], 'mutant': [71, 262, 2455, 2796, 3756], 'alleles': [72, 263, 1859, 2350, 2358, 2456, 2800], 'that': [73, 78, 264, 269, 574, 589, 1594, 1797, 3133, 3142, 3273], 'mirrorP.': [74, 265], 'variants': [76, 267], 'reveals': [77, 268], 'key': [80, 271, 599], 'mutation': [81, 147, 272, 338, 4011, 4148], 'Asn-108': [82, 273, 4012], '(Asn-83': [83, 274], 'gondii)': [86, 277], 'probably': [87, 150, 278, 341, 1381], 'confers': [88, 136, 279, 327], 'resistance': [89, 139, 178, 188, 280, 330, 369, 379, 1001, 1318, 1324, 1376, 1807, 2423, 3419, 3905, 4010, 4156], 'pyrimethamine': [91, 282, 1003, 1326, 1375, 1806, 2562, 3010, 3084, 3158, 3398, 3421, 3868, 4009], 'affecting': [93, 284], 'critical': [94, 285], 'interactions': [95, 286], 'ternary': [98, 289], 'complex.': [99, 290], 'Mutations': [100, 291], 'such': [101, 292, 1858, 3274], 'as': [102, 293, 579, 2002, 2206, 2220, 2277, 2650, 2682, 2840, 2878, 3089, 3794], 'Arg-59': [103, 294], '(T.': [104, 133, 295, 324], '36)': [106, 297], 'limited': [108, 299, 506], 'effect': [109, 300, 919, 2417], 'isolation,': [111, 302], 'but': [112, 142, 303, 333], 'combination': [114, 161, 305, 352, 827], 'with': [115, 164, 306, 355, 838, 1562, 1874, 1878, 1966, 2674, 2703, 2758, 3025, 3873, 3902, 3910, 4008, 4061, 4100], 'other': [116, 307, 666, 821, 1880, 4069], 'they': [118, 309], 'enhance': [119, 310], 'competitive': [121, 312], 'ability': [122, 313, 492], 'folate': [124, 155, 315, 346, 420, 577, 596, 603, 610, 755, 829, 846, 2373, 2759], 'increasing': [126, 317], 'speed': [128, 319], 'product': [130, 321], 'turnover.': [131, 322], 'Val-16': [132, 323], '10)': [135, 326], 'low': [137, 328, 3903], 'level': [138, 329, 3904], 'cycloguanil': [141, 332, 3013, 3160], 'hypersensitivity': [143, 334], 'pyrimethamine.': [145, 336], 'This': [146, 337, 587], 'precludes': [148, 339], 'Asn-108,': [149, 340], 'because': [151, 342, 1382], 'compression': [152, 343], 'binding': [156, 347, 3008, 3029, 3093, 3176], 'pocket': [157, 348], 'introduced': [158, 349, 2063, 2119, 2148, 2227, 2281], 'this': [160, 351, 1861, 1909, 2027, 2116, 2788, 4075], 'incompatible': [163, 354], 'enzyme': [165, 356, 626, 2017, 2668, 2739, 2768, 2793, 2816, 2882, 2908, 2947, 2972, 3131, 3810], 'function.': [166, 357], 'These': [167, 358, 488, 620, 1992, 2605, 3259], 'studies': [168, 359, 1993, 4162], 'permit': [169, 360], 'detailed': [170, 361], 'biochemical,': [171, 362], 'kinetic,': [172, 363], 'structural': [174, 365], 'drug': [177, 368, 428, 1317, 1940, 2015, 2422, 4155], 'reconstruction': [181, 372], 'probable': [184, 375], 'phylogeny': [185, 376], 'antifolate': [187, 378, 965, 3748], 'Among': [382], 'pathogens': [384], 'clinical': [386, 1369], 'significance,': [387], 'sp.': [392], 'share': [393], 'a': [394, 417, 676, 764, 842, 916, 968, 1854, 1946, 1967, 2003, 2072, 2305, 2480, 2617, 2841, 2849, 2853, 2859, 2903, 2951, 3090, 3322, 3415, 3752, 3778, 3795, 4072], 'common': [395, 1409, 3863, 4056, 4147], 'evolutionary': [396], 'history': [397], '(as': [398], 'members': [399], 'phylum': [402], 'Apicomplexa)': [403], '(1Levine': [404], 'N.D.': [405], 'J.': [406, 456, 462, 520, 555, 695, 714, 874, 880, 1223, 1225, 1243, 1270, 1339, 1351, 1435, 1441, 1471, 1501, 1503, 1506, 1647, 1782, 1894, 2133, 2330, 2388, 2406, 2595, 3645, 3647, 3665, 3692, 3827, 3921, 4020], 'Protozool.': [407, 2596], '1988;': [408, 1032, 1053, 1473, 2332, 2390, 3454, 3475, 3855, 3892, 3950, 3976, 3997, 4048, 4089, 4118, 4139, 4176], '35:': [409, 804, 2297, 2696, 2829], '518-520Crossref': [410], 'PubMed': [411, 469, 525, 548, 561, 704, 725, 739, 787, 806, 887, 954, 1035, 1056, 1074, 1093, 1114, 1135, 1156, 1168, 1197, 1212, 1252, 1277, 1297, 1344, 1448, 1479, 1533, 1615, 1632, 1656, 1671, 1690, 1706, 1731, 1761, 1788, 1827, 1842, 1903, 2094, 2252, 2299, 2335, 2393, 2411, 2444, 2525, 2544, 2586, 2600, 2644, 2698, 2831, 3045, 3057, 3103, 3118, 3185, 3226, 3372, 3457, 3478, 3496, 3515, 3536, 3557, 3578, 3590, 3619, 3634, 3674, 3699, 3719, 3838, 3858, 3895, 3932, 3953, 3979, 4000, 4031, 4051, 4092, 4121, 4142, 4179, 4196, 4213, 4232], 'Scopus': [412, 470, 526, 549, 562, 726, 740, 788, 807, 888, 955, 1036, 1057, 1075, 1094, 1115, 1136, 1157, 1169, 1198, 1213, 1231, 1253, 1278, 1298, 1345, 1449, 1480, 1511, 1534, 1616, 1633, 1672, 1691, 1707, 1732, 1762, 1789, 1828, 1843, 2095, 2253, 2300, 2336, 2394, 2445, 2526, 2545, 2587, 2601, 2645, 2699, 2832, 3046, 3058, 3073, 3104, 3119, 3186, 3227, 3373, 3458, 3479, 3497, 3516, 3537, 3558, 3579, 3591, 3620, 3635, 3653, 3675, 3700, 3720, 3839, 3859, 3896, 3933, 3954, 3980, 4001, 4032, 4052, 4093, 4122, 4143, 4180, 4197, 4214, 4233], '(91)': [413], 'Google': [414, 472, 528, 551, 564, 705, 728, 742, 790, 809, 890, 957, 1038, 1059, 1077, 1096, 1117, 1138, 1159, 1171, 1200, 1215, 1233, 1255, 1280, 1300, 1347, 1365, 1451, 1482, 1513, 1536, 1618, 1635, 1657, 1674, 1693, 1709, 1734, 1764, 1791, 1830, 1845, 1904, 2097, 2138, 2255, 2302, 2338, 2396, 2412, 2447, 2528, 2547, 2589, 2603, 2647, 2701, 2834, 3048, 3060, 3075, 3106, 3121, 3188, 3229, 3375, 3460, 3481, 3499, 3518, 3539, 3560, 3581, 3593, 3622, 3637, 3655, 3677, 3702, 3722, 3841, 3861, 3898, 3935, 3956, 3982, 4003, 4034, 4054, 4095, 4124, 4145, 4182, 4199, 4216, 4235], 'Scholar)': [415, 2139, 2256, 2303, 2339, 2448, 2648], 'vulnerability': [418], 'metabolism,': [421], 'which': [422, 2621, 3265, 3789], 'forms': [423], 'basis': [425, 2988], 'for': [426, 813, 971, 1411, 1553, 1596, 2005, 2053, 2125, 2218, 2257, 2342, 2609, 2652, 2666, 2813, 2863, 2914, 2917, 2979, 2982, 3006, 3027, 3164, 3174, 3278, 3393, 3797], 'effective': [427, 1417], 'treatment': [429, 815, 1370, 1410], '(2Brooks': [430, 848], 'R.G.': [431, 849], 'Remington': [432, 850], 'J.S.': [433, 851], 'Luft': [434, 453, 852, 871, 1432], 'B.': [435, 444, 454, 853, 862, 872, 1262, 1266, 1423, 1433, 1461, 3684, 3688], 'Antimicrob.': [436, 854], 'Agents': [437, 855], 'Annu.': [438, 856], '1987;': [439, 722, 857, 3835, 3929, 4028], '2:': [440, 858], '297-306Google': [441, 859], 'Scholar,': [442, 473, 529, 552, 706, 729, 791, 860, 891, 929, 939, 1039, 1060, 1078, 1097, 1118, 1139, 1160, 1172, 1201, 1216, 1234, 1256, 1281, 1348, 1483, 1514, 1619, 1636, 1658, 1675, 1694, 1710, 1765, 1831, 2397, 2529, 2590, 3049, 3061, 3107, 3461, 3482, 3500, 3519, 3540, 3561, 3582, 3594, 3623, 3638, 3656, 3678, 3703, 3936, 3983, 4125, 4183, 4200, 4217, 4236], '3Dannemann': [443, 861], 'McCutchan': [445, 863, 1424], 'J.A.': [446, 864, 1425, 2129], 'Israelski': [447, 865, 1426], 'D.': [448, 450, 866, 868, 1043, 1122, 1427, 1429, 1493, 1520, 1528, 3349, 3465, 3544, 3845, 3882, 3940, 3987, 4038, 4079, 4129, 4166], 'Antoniskis': [449, 867, 1428], 'Leport': [451, 869, 1430, 1490], 'C.': [452, 870, 1356, 1431, 1453, 1459, 1465, 1467, 1491], 'Nussbaum': [455, 873, 1434], 'Clumeck': [457, 875, 1436], 'N.': [458, 876, 1182, 1337, 1437, 1504, 3604], 'Morlat': [459, 877, 1438], 'P.': [460, 531, 878, 1180, 1439, 1640, 1677, 1775, 3602, 3768, 3816, 3876, 4219], 'Chiu': [461, 879, 1440], 'Ann.': [463, 881, 1442], 'Int.': [464, 882, 1443], 'Med.': [465, 883, 1227, 1272, 1340, 1444, 1472, 1507, 1784, 3649, 3694], '1992;': [466, 884, 1194, 1445, 3616], '116:': [467, 885, 1446], '33-43Crossref': [468, 886, 1447], '(287)': [471, 889, 1450, 1733], '4Hitchings': [474, 892], 'G.H.': [475, 477, 651, 653, 893, 895], 'Hitchings': [476, 652, 894], 'Inhibition': [478, 654, 896, 3153], 'Folate': [480, 656, 898], 'Metabolism': [481, 657, 899], 'Chemotherapy.': [483, 659, 901], 'Springer-Verlag,': [484, 660, 902], 'Berlin1983:': [485, 661, 903], '1-20Google': [486, 662, 904], 'Scholar).': [487, 565, 663, 743, 810, 905, 958, 1301, 1366, 1537, 1792, 1905, 2413, 2548, 2604, 2835, 3076, 3230, 3723], 'parasites': [489, 592, 1304, 1812, 2462, 2556], 'lack': [490, 2755], 'salvage': [494, 507], 'pyrimidine': [495], 'nucleosides': [496], 'host': [499], 'cell': [500], 'are': [502, 622, 984, 1320, 1379, 1388, 1911, 2029, 2153, 3023, 3138, 3145, 3276], 'capable': [503], 'only': [505, 2707, 3262], '(of': [508], 'uracil)': [509], 'their': [511], 'own': [512], 'pool': [513], 'metabolites': [515], '(5Schwartzman': [516], 'J.D.': [517], 'Pfefferkorn': [518, 2593], 'E.R.': [519, 2592], 'Parasitol.': [521, 544, 735, 783, 1089, 1110, 1193, 1208, 1248, 1293, 1628, 1667, 1686, 1702, 1838, 3511, 3532, 3615, 3630, 3670, 3715, 4192, 4209, 4228], '1981;': [522, 3100], '67:': [523], '150-158Crossref': [524], '(36)': [527, 563], '6Reyes': [530], 'Rathod': [532, 1699], 'P.K.': [533, 1700], 'Sanchez': [534], 'D.J.': [535, 708, 1103, 1522, 3525, 3821, 3915, 4014], 'Mrema': [536], 'J.E.': [537, 1068, 1162, 1625, 3490, 3584, 4189], 'Rieckmann': [538, 1259, 3681], 'K.H.': [539, 1260, 3682], 'Heidrich': [540], 'H.G.': [541], 'Mol.': [542, 1087, 1108, 1191, 1206, 1246, 1626, 1665, 1684, 1836, 3509, 3530, 3613, 3628, 3668, 4190, 4207, 4226], 'Biochem.': [543, 1088, 1109, 1192, 1207, 1247, 1627, 1666, 1685, 1837, 3052, 3065, 3180, 3221, 3510, 3531, 3614, 3629, 3669, 4191, 4208, 4227], '1982;': [545, 3067], '5:': [546, 927, 937, 1531], '275-290Crossref': [547], '(178)': [550], '7Iltzsch': [553], 'M.H.': [554], 'Euk.': [556], 'Microbiol.': [557], '1993;': [558, 698, 1508, 1650, 1824, 1897, 2091, 2249, 2541, 2641], '40:': [559], '24-28Crossref': [560], 'They': [566], 'therefore': [567, 1850, 3195], 'depend': [568], 'heavily': [569], 'on': [570, 825, 1997, 2366, 2421, 2986, 3291, 3747], 'de': [571], 'novobiosynthetic': [572], 'pathways': [573], 'consume': [575], 'reduced': [576], 'molecules': [578], 'methyl': [580], 'donors': [581], 'reactions': [583, 621, 2965], 'involving': [584], '1-carbon': [585], 'transfer.': [586], 'necessitates': [588], 'rapidly': [590, 3140], 'dividing': [591], 'maintain': [593], 'an': [594, 3292], 'abundant': [595], 'pool.': [597], 'enzymatic': [600, 2780], 'step': [601, 844], 'metabolism': [604], 'NADPH-dependent': [607], 'reduction': [608, 615], 'H2-folate': [612, 617, 773, 2915, 2980], 'further': [614], 'H4-folate.': [619], 'catalyzed': [623], '(DHFR)': [629], '1The': [630, 640], 'abbreviations': [631, 641], 'used': [632, 642, 907, 2025, 2052, 2341, 2608, 3234], 'are:': [633, 643], 'DHFR,': [634, 644], 'reductase;': [636, 646], 'TS,': [637, 647], 'thymidylate': [638, 648, 690], 'synthase.': [639, 649], '(4Hitchings': [650], 'As': [664, 3410], 'protozoa': [667], '(and': [668, 1982, 3422], 'plants),': [669], 'DHFR': [670, 746, 777, 833, 1013, 1542, 1799, 1883, 1918, 1935, 2110, 2203, 2233, 2273, 2836, 2874, 3156, 3434, 3783, 4066], 'occupies': [671], 'NH2-terminal': [673], 'portion': [674], 'homodimeric': [677], 'bifunctional': [678, 1584], 'protein': [679, 766, 2710, 2733, 3435], 'bothToxoplasma': [681], 'Plasmodium,': [683], 'fused': [684], 'at': [685, 2771, 2804, 2845, 2868, 2890, 2929, 2973, 4074], 'COOH': [687], 'terminus': [688], 'synthase': [691], '(TS)': [692], '(8Roos': [693, 1892], 'D.S.': [694, 797, 941, 1041, 1141, 1287, 1816, 1835, 1893, 2083, 2241, 2290, 2431, 2512, 2533, 2573, 2633, 2689, 2822, 3463, 3563, 3709, 3843, 3880, 3938, 3985, 4036, 4077, 4127, 4164], 'Biol.': [696, 950, 1360, 1648, 1895, 2440, 2521, 2582, 3368], 'Chem.': [697, 1649, 1896], '268:': [699, 1651, 1898], '6269-6280Abstract': [700, 1899], 'Full': [701, 1476, 1653, 1900, 3070], 'Text': [702, 1477, 1654, 1901, 3071], 'PDF': [703, 1478, 1655, 1902, 3072], '9Bzik': [707], 'Li': [709, 1104, 3526, 3822, 3916, 4015], 'W.B.': [710, 3823, 3917, 4016], 'Horii': [711, 1663, 3824, 3918, 4017, 4205], 'Inselburg': [713, 1106, 3528, 3826, 3920, 4019], 'Proc.': [715, 1025, 1046, 1125, 1146, 1721, 1751, 1817, 2084, 2242, 2534, 2634, 3447, 3468, 3547, 3568, 3828, 3848, 3885, 3922, 3943, 3969, 3990, 4021, 4041, 4082, 4111, 4132, 4169], 'Natl.': [716, 1026, 1047, 1126, 1147, 1722, 1752, 1818, 2085, 2243, 2535, 2635, 3448, 3469, 3548, 3569, 3829, 3849, 3886, 3923, 3944, 3970, 3991, 4022, 4042, 4083, 4112, 4133, 4170], 'Acad.': [717, 1027, 1048, 1127, 1148, 1723, 1753, 1819, 2086, 2244, 2536, 2636, 3449, 3470, 3549, 3570, 3830, 3850, 3887, 3924, 3945, 3971, 3992, 4023, 4043, 4084, 4113, 4134, 4171], 'Sci.': [718, 1028, 1049, 1128, 1149, 1724, 1754, 1820, 2087, 2245, 2537, 2637, 3066, 3450, 3471, 3550, 3571, 3831, 3851, 3888, 3925, 3946, 3972, 3993, 4024, 4044, 4085, 4114, 4135, 4172], 'U.': [719, 1029, 1050, 1129, 1150, 1725, 1755, 1821, 2088, 2246, 2538, 2638, 3451, 3472, 3551, 3572, 3832, 3852, 3889, 3926, 3947, 3973, 3994, 4025, 4045, 4086, 4115, 4136, 4173], 'S.': [720, 1030, 1051, 1086, 1130, 1151, 1174, 1178, 1283, 1457, 1726, 1756, 1822, 2089, 2247, 2399, 2539, 2639, 3051, 3179, 3220, 3452, 3473, 3508, 3552, 3573, 3596, 3600, 3705, 3833, 3853, 3890, 3927, 3948, 3974, 3995, 4026, 4046, 4087, 4116, 4137, 4174], 'A.': [721, 1031, 1052, 1131, 1152, 1205, 1245, 1727, 1757, 1823, 2090, 2248, 2540, 2640, 3350, 3453, 3474, 3553, 3574, 3627, 3667, 3834, 3854, 3891, 3928, 3949, 3975, 3996, 4027, 4047, 4088, 4117, 4138, 4175], '84:': [723, 1295, 1474, 3717, 3836, 3930, 4029], '8360-8364Crossref': [724, 3837, 3931, 4030], '(233)': [727, 3840, 3934, 4033], '10Ivanetich': [730], 'K.M.': [731, 779, 3363], 'Santi': [732, 780, 800, 1609, 1645, 1682, 1719, 2293, 2692, 2825, 4224], 'D.V.': [733, 781, 801, 1610, 1646, 1683, 1720, 2294, 2693, 2826, 4225], 'Exp.': [734, 782, 1292, 1701, 1783, 3714], '1990;': [736, 784, 1111, 1132, 1153, 1165, 1612, 3533, 3554, 3575, 3587], '70:': [737, 785], '367-371Crossref': [738, 786], '(38)': [741, 789], 'TS': [744, 775, 1885], 'catalyze': [747], 'sequential': [748], 'steps': [749], 'regeneration': [752], 'methyl-charged': [754], 'molecules,': [756], 'coupling': [758], 'these': [760, 910, 3743], 'two': [761, 911, 3151], 'activities': [762], 'within': [763], 'single': [765], 'thought': [768], 'facilitate': [770], 'channeling': [771], '(10Ivanetich': [778], '11Trujillo': [792], 'M.': [793, 923, 1099, 1186, 1516, 1696, 2286, 2685, 2818, 3521, 3608], 'Donald': [794, 942, 2287, 2432, 2513, 2574, 2686, 2819], 'R.G.K.': [795, 943, 1814, 1833, 2081, 2239, 2288, 2433, 2514, 2531, 2575, 2631, 2687, 2820], 'Roos': [796, 1815, 1834, 2082, 2240, 2289, 2532, 2632, 2688, 2821], 'Greene': [798, 2291, 2690, 2823], 'P.J.': [799, 2292, 2691, 2824], 'Biochemistry.': [802, 1611, 2295, 2694, 2827, 3099], '1996;': [803, 1274, 1294, 1362, 1687, 1758, 2296, 2695, 2828, 3696, 3716, 4229], '6366-6374Crossref': [805, 2298, 2697, 2830], '(61)': [808, 2301, 2700, 2833], 'Antifolate': [811], 'chemotherapy': [812], 'malaria,': [817], 'toxoplasmosis,': [818], 'many': [820], 'infectious': [822], 'diseases': [823], 'relies': [824], 'analogs': [830], 'inhibit': [832, 841], '(pyrimethamine,': [834], 'trimethoprim,': [835], 'cycloguanil,': [836], 'etc.)': [837], 'sulfonamides': [839], 'prior': [843], 'biosynthesis': [847], 'When': [906], 'combination,': [909], 'classes': [912], 'drugs': [914], 'exhibit': [915], 'pronounced': [917], 'synergistic': [918], '(12Eyles': [920], 'D.E.': [921, 931], 'Coleman': [922], 'Antibiot.': [924, 934], 'Chemother.': [925, 935], '1955;': [926, 936], '529-539Google': [928], '13Eyles': [930], 'Jones': [932], 'F.E.': [933], '731-734Google': [938], '14Roos': [940], 'Morrissette': [944, 2434, 2515, 2576], 'N.S.': [945, 2435, 2516, 2577], 'Moulton': [946, 2436, 2517, 2578], 'A.L.C.': [947, 2437, 2518, 2579], 'Methods': [948, 2438, 2519, 2580], 'Cell': [949, 2439, 2520, 2581], '1994;': [951, 1209, 1228, 1668, 1839, 2441, 2522, 2583, 3369, 3631, 3650, 4210], '45:': [952, 1630, 2442, 2523, 2584, 4194], '27-63Crossref': [953, 2443, 2524, 2585], '(498)': [956, 2446, 2527, 2588], 'virtue': [960], 'effectiveness,': [963], 'however,': [964, 1403], 'therapy': [966], 'establishes': [967], 'robust': [969], 'selection': [970], 'resistant': [972], 'microbes.': [973], 'Mechanisms': [974], 'acquired': [976, 1374], 'resistance,': [977, 983, 3749], 'metabolic': [980], 'cost': [981], 'issues': [985], 'considerable': [987], 'importance': [988], 'medical': [990], 'biological': [992], 'science.': [993], 'close': [995], 'correlation': [996, 3417], 'has': [997, 1548, 1954], 'been': [998, 1549, 1888], 'noted': [999, 3411], 'between': [1000, 2937, 2997, 3380, 3418], '(and/or': [1004], 'cycloguanil)': [1005, 3423], 'point': [1008, 1919], 'malarial': [1012], 'gene': [1014], '(15Cowman': [1015, 3437], 'A.F.': [1016, 1124, 1268, 1335, 1606, 3438, 3546, 3690, 3960, 4102], 'Morry': [1017, 3439, 3961, 4103], 'M.J.': [1018, 1518, 3440, 3962, 4104], 'Biggs': [1019, 3441, 3963, 4105], 'B.A.': [1020, 3442, 3964, 4106], 'Cross': [1021, 3443, 3965, 4107], 'G.A.M.': [1022, 3444, 3966, 4108], 'Foote': [1023, 3445, 3967, 4109], 'S.J.': [1024, 1120, 1621, 3446, 3542, 3968, 4110, 4185], '85:': [1033, 1054, 1704, 3455, 3476, 3856, 3893, 3951, 3977, 3998, 4049, 4090, 4119, 4140, 4177], '9109-9113Crossref': [1034, 3456, 3978, 4120], '(438)': [1037, 3459, 3981, 4123], '16Peterson': [1040, 3462, 3937, 3984, 4126], 'Walliker': [1042, 3464, 3844, 3881, 3939, 3986, 4037, 4078, 4128, 4165], 'Wellems': [1044, 1144, 1749, 3466, 3566, 3846, 3883, 3941, 3988, 4039, 4080, 4130, 4167], 'T.E.': [1045, 1145, 1750, 3467, 3567, 3847, 3884, 3942, 3989, 4040, 4081, 4131, 4168], '9114-9118Crossref': [1055, 3477, 3857, 3894, 3952, 3999, 4050, 4091, 4141, 4178], '(528)': [1058, 3480, 3860, 3897, 3955, 4002, 4053, 4094, 4144, 4181], '17Snewin': [1061, 3483], 'V.A.': [1062, 3484], 'England': [1063, 3485], 'S.M.': [1064, 3486], 'Sims': [1065, 1622, 3487, 4186], 'P.F.': [1066, 1623, 3488, 4187], 'Hyde': [1067, 1624, 3489, 4188], 'Gene': [1069, 3491], '(Amst.).': [1070, 3492], '1989;': [1071, 1090, 2135, 3493, 3512], '76:': [1072, 3494], '41-52Crossref': [1073, 3495], '(96)': [1076, 3498], '18Zolg': [1079, 3501], 'J.W.': [1080, 1107, 3502, 3529], 'Plitt': [1081, 3503], 'J.R.': [1082, 3504], 'Chen': [1083, 3505], 'G.X.': [1084, 3506], 'Palmer': [1085, 3507], '36:': [1091, 3513], '253-263Crossref': [1092, 3514], '(106)': [1095, 3517], '19Tanaka': [1098, 3520], 'Gu': [1100, 3522], 'H.': [1101, 3523], 'Bzik': [1102, 3524], 'W.': [1105, 1602, 1638, 1679, 1712, 3527, 4221, 4238], '39:': [1112, 3534], '127-134Crossref': [1113, 3535], '(39)': [1116, 3538], '20Foote': [1119, 3541], 'Galatis': [1121, 3543], 'Cowman': [1123, 1267, 1605, 3545, 3689], '87:': [1133, 1154, 3555, 3576], '3014-3017Crossref': [1134, 3556], '(262)': [1137, 3559], '21Peterson': [1140, 3562], 'Milhous': [1142, 3564], 'W.K.': [1143, 3565], '3018-3022Crossref': [1155, 3577], '(378)': [1158, 3580], '22Hyde': [1161, 3583], 'Pharmacol.': [1163, 3053, 3181, 3222, 3585], 'Ther.': [1164, 3586], '48:': [1166, 3588], '45-59Crossref': [1167, 3589], '(124)': [1170, 3592], '23Thaithong': [1173, 3595], 'Chan': [1175, 3597], 'S.W.': [1176, 3598], 'Songsomboon': [1177, 3599], 'Wilairat': [1179, 3601], 'Seesod': [1181, 3603], 'Sueblinwong': [1183, 3605], 'Goman': [1185, 3607], 'Ridley': [1187, 3609], 'R.': [1188, 1357, 1487, 1499, 1526, 1604, 1642, 1716, 2401, 3610], 'Beale': [1189, 3611], 'G.': [1190, 1291, 1660, 3612, 3713, 4202], '52:': [1195, 3617], '149-158Crossref': [1196, 3618], '(64)': [1199, 3621], '24Cheng': [1202, 3624], 'Q.': [1203, 3625], 'Saul': [1204, 3626], '65:': [1210, 3632], '361-363Crossref': [1211, 3633], '(31)': [1214, 1634, 3636, 4198], '25Basco': [1217, 3639], 'L.K.': [1218, 1236, 1353, 3640, 3658], 'Ramiliar': [1219, 3641], 'O.': [1220, 1289, 3642, 3711], 'Le': [1221, 1241, 3643, 3663], 'Bas': [1222, 3644], 'Am.': [1224, 1269, 1470, 3646, 3691], 'Trop.': [1226, 1271, 3648, 3693], '10:': [1229, 3651], '193-199Crossref': [1230, 3652], '(40)': [1232, 1535, 3654], '26Basco': [1235, 3657], 'Pecoulas': [1237, 3659], 'P.E.': [1238, 1355, 3660], 'Wilson': [1239, 3661], 'C.M.': [1240, 3662], 'bas': [1242, 3664], 'Mazabraud': [1244, 3666], '1995;': [1249, 1341, 3671], '69:': [1250, 3672], '135-138Crossref': [1251, 3673], '(162)': [1254, 3676], '27Reeder': [1257, 3679], 'J.C.': [1258, 3680], 'Genton': [1261, 3683], 'Lorry': [1263, 3685], 'K.': [1264, 1662, 3686, 4204], 'Wines': [1265, 3687], 'Hyg.': [1273, 3695], '55:': [1275, 3697], '209-213Crossref': [1276, 3698], '(109)': [1279, 3701], '28Zindrou': [1282, 3704], 'Nguyen': [1284, 1286, 3706, 3708], 'P.D.': [1285, 3707], 'Skold': [1288, 3710], 'Swedberg': [1290, 3712], '56-64Crossref': [1296, 3718], '(33)': [1299, 3721], 'Because': [1302], 'malaria': [1303, 1332, 1547, 1923, 3425, 4151], 'may': [1305], 'be': [1306, 1391, 3791], 'spread': [1307], 'one': [1309, 1394, 2926], 'individual': [1310, 1395], 'another': [1312], 'via': [1313], 'mosquito': [1315], 'vector,': [1316], 'disseminated': [1321], 'rapidly.': [1322], 'Widespread': [1323], 'threatens': [1327], 'efforts': [1328], 'manage': [1330], 'cerebral': [1331], 'worldwide': [1333], '(29Cowman': [1334], 'Austr.': [1336], 'Z.': [1338, 3361], '25:': [1342], '837-844Crossref': [1343], '(20)': [1346], '30Le': [1349], 'bras': [1350], 'Basco': [1352], 'dePecoulas': [1354], 'Seances': [1358], 'Soc.': [1359], 'Fil.': [1361], '190:': [1363], '471-485PubMed': [1364], 'Reports': [1367], 'failures': [1371], 'caused': [1372], 'rare,': [1380], 'humans': [1387], 'unlikely': [1389], 'transmitted': [1392], 'another.': [1397], 'Should': [1398], 'antifolate-resistant': [1399], 'emerge,': [1402], 'would': [1405], 'threaten': [1406], 'most': [1408], 'acute': [1412], 'toxoplasmosis': [1413], 'sole': [1416], 'chemoprophylaxis': [1418], 'immunocompromised': [1420], 'patients': [1421], '(3Dannemann': [1422], 'Scholar,31Leport': [1452], 'Raffi': [1454], 'F.': [1455, 2131], 'Matheron': [1456], 'Katlama': [1458], 'Regnier': [1460], 'Saimot': [1462], 'A.G.': [1463], 'Marche': [1464], 'Vedrenne': [1466], 'Vilde': [1468], 'J.L.': [1469, 1524], '94-100Abstract': [1475], '(212)': [1481], '32Luft': [1484], 'B.J.': [1485], 'Hafner': [1486], 'Korzan': [1488], 'A.H.': [1489], 'Antoniski': [1492], 'Bosler': [1494], 'E.': [1495, 1597, 2047, 2224, 2310, 2659, 3357], 'Bourland': [1496], 'D.D.': [1497], 'Uttamchandani': [1498], 'Fuhrer': [1500], 'Jacobsin': [1502], 'Engl.': [1505], '529:': [1509], '995-1000Crossref': [1510], '(366)': [1512], '33Tenant-Flowers': [1515], 'Boyle': [1517], 'Carey': [1519], 'Marriott': [1521], 'Harkness': [1523], 'Penny': [1525], 'Cooper': [1527], 'AIDS.': [1529], '1991;': [1530, 1629, 4193], '311-315Crossref': [1532], 'The': [1538, 1906, 2354, 2549, 3283, 3309], 'precise': [1539], 'role': [1540, 1938], 'sequence': [1543, 1872, 2112, 2162, 3436], 'difficult': [1550], 'ascertain': [1552], 'several': [1554], 'reasons': [1555], 'including:': [1556], '(i)': [1557], 'difficulties': [1559], 'working': [1561], 'Plasmodiumparasites;': [1563], '(ii)': [1564], 'difficulty': [1566, 1581], 'maintaining': [1568], 'clones': [1571, 1593], 'spanning': [1572], 'highly': [1574], 'A/T-rich': [1575], 'DHFR-TS': [1577, 1586, 1866, 1970, 2079, 2419, 2709, 2799, 2894, 3022, 3288, 3732, 3759, 3809], 'gene;': [1578], '(iii)': [1579], 'expressing': [1583], 'Escherichia': [1588], 'coli': [1589, 1598, 2048, 2225, 2311], '(even': [1590], 'using': [1591, 1972, 2140, 2304, 2858, 3296, 3321, 3337, 3404, 3777], 'synthetic': [1592, 2143], 'optimize': [1595], 'codon': [1599, 2070, 2625], 'usage)': [1600], '(34Sirawaraporn': [1601], 'Sirawaraporn': [1603, 1641, 1678, 1715, 4220], 'Yuthavong': [1607, 1643, 1680, 1717, 4222], 'Y.': [1608, 1644, 1681, 1718, 1746, 4223], '29:': [1613], '10779-10785Crossref': [1614], '(67)': [1617], '35Hall': [1620, 4184], '317-330Crossref': [1631, 4195], '36Sirawaraporn': [1637], 'Prapunwattana': [1639], '21637-21644Abstract': [1652], '37Sano': [1659, 4201], 'Morimatsu': [1661, 4203], '63:': [1669, 1840, 4211], '265-273Crossref': [1670, 4212], '(35)': [1673, 4215], '38Prapunwattana': [1676, 4218], '83:': [1688, 4230], '93-106Crossref': [1689, 4231], '(30)': [1692, 4234], '39Hekmat-Nejad': [1695], 'Lee': [1697], 'P.C.': [1698], '1997;': [1703, 1728, 1785], '303-305Crossref': [1705], '(15)': [1708], '40Sirawaraporn': [1711, 4237], 'Sathitkul': [1713], '94:': [1729], '1124-1129Crossref': [1730], 'Scholar);': [1735, 3122], '(iv)': [1737], 'inefficiency': [1739], 'molecular': [1741, 3302], 'systems': [1743], 'forPlasmodium': [1744], '(41Wu': [1745], 'Kirkman': [1747], 'L.A.': [1748], '93:': [1759], '1130-1134Crossref': [1760], '(332)': [1763], '42van': [1766], 'der': [1767], 'Wel': [1768], 'A.M.': [1769, 1771], 'Tomas': [1770], 'Kocken': [1772], 'C.H.': [1773], 'Malhotra': [1774], 'Janse': [1776], 'C.J.': [1777], 'Waters': [1778], 'A.P.': [1779], 'Thomas': [1780], 'A.W.': [1781], '185:': [1786, 3043], '1499-1503Crossref': [1787], '(74)': [1790, 3120], 'demonstrated': [1795], 'previously': [1796, 2812], 'certain': [1798, 2006, 3080], 'observed': [1801, 3729, 4005], 'Fansidar-resistantPlasmodium': [1803], 'confer': [1805], 'transgenic': [1809, 2260], '(43Donald': [1813, 2080, 2238, 2630], '90:': [1825, 2092, 2250, 2542, 2642], '11703-11707Crossref': [1826, 2093, 2251, 2543, 2643], '(280)': [1829, 2096, 2254, 2546, 2646], '44Donald': [1832], '243-253Crossref': [1841], '(75)': [1844], 'Scholar),': [1846, 2098, 2702, 3189, 3376], 'we': [1848, 3750], 'chosen': [1851], 'wider': [1855], 'variety': [1856, 1968], 'experimentally': [1862], 'accessible': [1863], 'system.': [1864], 'shares': [1867], 'greater': [1868], 'primary': [1869, 3310], 'amino': [1870, 3428, 3744], 'acid': [1871, 3429, 3745, 3819], 'identity': [1873], 'Toxoplasmathan': [1875], 'does': [1877, 3085], 'any': [1879], 'species': [1881, 4070], 'whose': [1882], 'genes': [1886], 'examined': [1889], 'date': [1891], 'objectives': [1907], 'study': [1910, 2028], 'clarify': [1913], 'mechanistic': [1915], 'effects': [1916, 3741], 'gain': [1926], 'insights': [1927], 'into': [1928, 2120, 2282, 2489, 3799], 'characteristics': [1931], 'susceptibility': [1941], 'resistance.': [1943], 'suitable': [1947], 'set': [1948], 'proven': [1955], 'vivo': [1960], 'vitrothe': [1963], 'phenotypes': [1964], 'associated': [1965, 3872, 3909], 'yeast)': [1983], 'extend': [1994], 'previous': [1995], 'findings': [1996], 'suitability': [1999], 'model': [2004], 'aspects': [2007], 'ofPlasmodium': [2008], 'biology,': [2009], 'revealing': [2010], 'how': [2011], 'interaction': [2013], 'disrupted': [2019], 'naturally': [2021], 'occurring': [2022], 'mutations.': [2023], 'Vectors': [2024], 'shown': [2030, 2154, 2163, 3734], 'Fig.': [2032], '1.': [2033], 'Manipulation': [2034], 'DNA': [2037, 2469], 'was': [2041, 2051, 2062, 2113, 2340, 2364, 2626, 2711, 2748, 2761, 2769, 2782, 2838, 2999, 3289, 3383, 3400, 3774], 'accomplished': [2042, 2728], 'according': [2043], 'standard': [2045], 'protocols.': [2046], 'strain': [2049, 2312, 2661], 'DH5α': [2050], 'routine': [2054], 'cloning': [2055], 'plasmid': [2057, 2101, 2117, 2236, 2352, 2468, 3780], 'propagation.': [2058], 'uniqueBamHI': [2060], 'site': [2061], 'slightly': [2064, 2306], 'upstream': [2065], 'ATG': [2068, 2623], 'initiation': [2069, 2624], 'expression': [2074, 2219, 2258, 2669], 'vector': [2075, 2123, 2217, 2284, 2656], 'containing': [2076], 'produce': [2100, 2885], 'placZDHFR-TS.': [2102], '1-kilobase': [2104], 'BamHI-EcoRI': [2105], 'fragment': [2106], 'harboring': [2107, 2453], 'complete': [2109, 3808], 'coding': [2111, 2161, 3787], 'excised': [2114, 3792], 'pKS(−)': [2122], '(Stratagene)': [2124], 'site-directed': [2126], 'mutagenesis': [2127], '(45McClary': [2128], 'Whitney': [2130], 'Geisselsoder': [2132], 'BioTechniques.': [2134], '7:': [2136, 3068], '282-289PubMed': [2137], 'following': [2142, 2705, 3125], 'oligonucleotides': [2144], '(underlined': [2145], 'nucleotides': [2146], 'indicate': [2147], 'mutations,': [2149, 2190], 'mutated': [2151, 2205, 2627], 'codons': [2152], 'bold):': [2156], '5′-tctacggggcgttgtcggatccgggaagATGCAGAAACC-3′': [2157], '(upstream': [2158], 'BamHI': [2159], 'site;': [2160], 'uppercase);': [2165], '5′-GTGTCTGGTCGTCGTGATGACCCCCAAGA-3′': [2166], '(Val-10);': [2167], '5′-GATTTCAAACACTTTCG': [2168], 'TCGTGTGACAAAAACGGAC-3′': [2169], '(Arg-36);': [2170], '5′-ATGGGACGGAAAAACTGGGAAAGCATGCCT-3′': [2171], '(Asn-83);': [2172], '5′-ATGGGACGGAAAAGCTGGGAAAGCATGCCT-3′': [2173], '(Ser-83);': [2174], '5′-GGTACCCTACGACTCCGTGGTTCTCGAGAAG-3′': [2175], '(Ser-245).': [2176], 'Polymerase': [2177], 'chain': [2178], 'reaction-based': [2179], 'methods': [2180], 'were': [2181, 2194, 2211, 2280, 2449, 2470, 2563, 2607, 2664, 2678, 2727, 2741, 2801, 2899, 2919, 2966, 2984, 3194, 3233, 3260, 3319, 3331], 'avoided': [2182], 'minimize': [2184], 'possibility': [2186], 'introducing': [2188], 'unintended': [2189], 'all': [2192], 'mutants': [2193, 2275, 2898, 3762], 'confirmed': [2195, 2749, 2762, 4157], 'sequencing': [2197], 'across': [2198], 'entire': [2200], 'targeted': [2201], 'region.': [2202], 'sequences,': [2204], 'described': [2207, 2278, 2683], 'text,': [2210], 'then': [2212], 'returned': [2213], 'placZDHFR-TS': [2216], 'transcriptional': [2221], 'fusions': [2222], 'place': [2229], 'wild-type': [2232, 2427, 2815, 2946, 3765, 3864, 4057, 4065], 'locus': [2234], 'pDHFR-TSc3': [2237, 2615], 'parasites.': [2263], 'For': [2264], 'overexpression': [2265], 'bacteria': [2267], 'purification': [2269, 2677], 'enzyme,': [2272, 3205], 'domain': [2274, 3786], '(produced': [2276], 'above)': [2279], 'apET15b-based': [2283], '(11Trujillo': [2285, 2684, 2817], 'smaller': [2307], 'cassette': [2308, 3796], '(AgeI-XhoI).': [2309], 'LH-18': [2313], '(Δlac-pro': [2314], 'supE': [2315], 'hsdR5': [2316], 'thyA': [2317], 'Δfol::Kan': [2318], 'F′lac': [2319], '[Iq-ZΔM15]': [2320], '+': [2321, 2463, 2504], 'pro': [2322], '+)': [2323], '(46Howell': [2324, 2382], 'E.E.': [2325, 2383], 'Forster': [2326, 2328, 2384, 2386], 'P.G.': [2327, 2385], 'L.M.': [2329, 2387], 'Bacteriol.': [2331, 2389, 2407], '170:': [2333, 2391], '3040-3045Crossref': [2334, 2392], '(44)': [2337, 2395], 'various': [2347, 2454, 2559, 3212], 'gondiiDHFR-TS': [2349], '(in': [2351], 'placZDHFR-TS).': [2353], 'capacity': [2355], 'mutagenized': [2357], 'complement': [2360], 'fol': [2362], '−phenotype': [2363], 'determined': [2365, 2742, 2802, 2920], 'minimal': [2367], 'media': [2368], 'absence': [2371], 'supplements': [2374], '(methionine,': [2375], 'glycine,': [2376], 'thymidine,': [2377], 'adenine,': [2378], 'pantothenic': [2380], 'acid)': [2381], '47Singer': [2398], 'Ferone': [2400], 'Walton': [2402], 'L.': [2403, 2405, 3341], 'Elwell': [2404], '1985;': [2408], '164:': [2409], '470-472Crossref': [2410], 'To': [2414, 3738], 'determine': [2415, 3236], 'tissue': [2425], 'culture,': [2426], 'RH-strain': [2428], 'tachyzoites': [2429], '(14Roos': [2430, 2511, 2572], 'transfected': [2450, 2555], 'withpDHFR-TSc3': [2451], 'vectors': [2452, 3805], 'interest.': [2458], 'Two': [2459], '×': [2460, 3256], '107': [2461], '30': [2464], 'μg': [2465], 'CsCl-purified': [2467], 'mixed': [2471], '2-mm': [2473], 'gap': [2474], 'electroporation': [2475], 'cuvettes': [2476], '(BTX),': [2477], 'subjected': [2478], '∼0.25-msec': [2481], 'pulse': [2482], '(1.5': [2483], 'kEV,': [2484], '24': [2485], 'ohms)': [2486], 'inoculated': [2488], 'confluent': [2490], 'monolayers': [2491], 'human': [2493], 'foreskin': [2494], 'fibroblast': [2495], 'cells': [2496], '24-well': [2498], 'plates': [2499], 'modified': [2501], "Eagle's": [2502], 'medium': [2503], '1%': [2505], 'heat-inactivated,': [2506], 'dialyzed': [2507], 'fetal': [2508], 'bovine': [2509], 'serum': [2510], '43Donald': [2530], 'viability': [2550], 'proliferation': [2552], 'transiently': [2554], 'grown': [2557], 'concentrations': [2560, 2734, 2954], 'measured': [2564, 2839], '24–36': [2565], 'h': [2566], 'post-transfection': [2567], '[3H]uracil': [2569], 'uptake': [2570], 'assay': [2571], '48Pfefferkorn': [2591], 'L.C.': [2594], '1977;': [2597], '24:': [2598, 3055, 3183, 3224], '449-453Crossref': [2599], '(152)': [2602], 'data': [2606], 'calculation': [2610, 3033], 'IC50': [2612, 3198], 'values.': [2613, 3282], 'Wild-type': [2614], 'null': [2618], 'allele': [2619, 4058], 'TTG': [2629], 'served': [2649], 'controls': [2651], 'transfection': [2653], 'studies.': [2654], 'Plasmid': [2655], 'pET15b': [2657], 'colihost': [2660], 'BL21(DE3)PLysS': [2662], '(Novagen)': [2663], 'employed': [2665], '2-liter': [2671], 'cultures.': [2672], 'Induction': [2673], 'isopropyl-1-thio-β-d-galactopyranoside': [2675], 'carried': [2679, 3775], 'out': [2680, 3776], 'essentially': [2681], 'modifications:': [2706], 'soluble': [2708], 'after': [2713], 'induction;': [2714], 'both': [2715], 'affinity': [2716], 'chromatography': [2717, 2724], '(on': [2718], 'methotrexate-agarose;': [2719], 'Sigma)': [2720], 'anion': [2722], 'exchange': [2723], '(DE52;': [2725], 'Whatman)': [2726], 'gravity': [2730], 'flow;': [2731], 'crude': [2736], 'preparations': [2740], 'Bradford': [2744], 'assay.': [2745], 'Enzyme': [2746], 'purity': [2747], 'SDS-polyacrylamide': [2751], 'gel': [2752], 'electrophoresis,': [2753], 'contamination': [2757], 'derivatives': [2760], 'assayingA': [2764], '280/320': [2765], 'ratios.': [2766], 'Purified': [2767, 2893], 'stored': [2770], '−20': [2772], '°C': [2773, 2806], '10%': [2775], 'glycerol;': [2776], 'no': [2777], 'loss': [2778], 'activity': [2781, 2837, 2875], 'detected': [2783], 'during': [2784, 2852], 'course': [2786], 'study.': [2789], 'Kinetic': [2790, 2977], 'parameters': [2791], 'produced': [2794], 'spectrophotometrically': [2803], '25': [2805, 2891], 'under': [2807, 3200, 3246, 3264], 'steady-state': [2809, 3134], 'conditions': [2810, 3202, 3247, 3263], 'established': [2811, 3162], 'decrease': [2842], 'absorbance': [2844], '340': [2846, 2869], 'nm': [2847, 3204], '1.0-cm': [2850], 'cuvette': [2851], '2–3-min': [2854], 'interval': [2855], '(results': [2856], 'calculated': [2857, 2985, 3196], 'molar': [2860], 'extinction': [2861], 'coefficient': [2862], 'NADPH': [2864, 2918, 2983], '12,000': [2866], 'm−1cm−1': [2867], 'nm).': [2870], 'One': [2871], 'unit': [2872], 'defined': [2877], 'amount': [2880], 'necessary': [2883], '1': [2886], 'μmol': [2887], 'product/min': [2889], '°C.': [2892], 'fractions': [2895], 'different': [2897], 'assumed': [2900], 'retain': [2902], 'uniform': [2904], 'percentage': [2905], 'active': [2907], '(∼90%).': [2909], 'Apparent': [2910], 'K': [2911, 2943, 2959, 3003, 3191, 3257], 'm': [2912, 2944, 2960], 'values': [2913, 2978, 3005, 3193, 3199], 'while': [2921], 'keeping': [2922], 'concentration': [2924, 3149], 'substrate': [2927], 'constant': [2928], '100': [2930, 3206], 'μm': [2931, 3207], 'varying': [2933], 'other,': [2935], 'initially': [2936], '0.5': [2938], '50': [2940, 3209], 'times': [2941, 2956], 'subsequently': [2949], 'over': [2950, 3150], 'range': [2952], 'encompassing': [2953], '0.5–50': [2955], 'estimated': [2958], 'mutant.': [2963], 'All': [2964, 4063], 'initiated': [2967], 'addition': [2970], 't': [2974], '=': [2975, 3254], '0.': [2976], 'three': [2990], 'six': [2992], 'independent': [2993], 'experiments': [2994, 2998], '(observed': [2995], 'variation': [2996], 'always': [3000], '≤': [3001], '15%).': [3002], 'i': [3004, 3192, 3281], '(Sigma)': [3011], '(Jacobus': [3014], 'Pharmaceutical': [3015], 'Co.,': [3016], 'Princeton': [3017], 'NJ)': [3018], 'wild-typeT.': [3020], 'consistent': [3024], 'expectations': [3026], 'tight': [3028, 3092, 3175], 'inhibitors,': [3030], 'complicating': [3031], 'inhibition': [3035, 3126, 3137, 3172, 3240], 'constants': [3036, 3173], '(49Morrison': [3037], 'J.F.': [3038, 3063, 3111], 'Biochim.': [3039, 3112], 'Biophys.': [3040, 3113], 'Acta.': [3041, 3114], '1969;': [3042], '269-286Crossref': [3044], '(706)': [3047], '50Cha': [3050, 3219], '1975;': [3054, 3182, 3223], '2177-2185Crossref': [3056, 3184, 3225], '(446)': [3059, 3187, 3228], '51Morrison': [3062], 'Trends': [3064], '102-105Abstract': [3069], '(492)': [3074], 'In': [3077], 'contrast': [3078], 'antifolates': [3081], '(e.g.methotrexate;': [3082], '51),': [3083], 'not': [3086], 'typically': [3087], 'behave': [3088], 'slow': [3091], 'inhibitor': [3094, 3148, 3213, 3399], '(52Baccanari': [3095], 'D.P.': [3096], 'Joyner': [3097], 'S.S.': [3098], '20:': [3101], '1710-1716Crossref': [3102], '(45)': [3105], '53Stone': [3108], 'S.R.': [3109], 'Morrison': [3110], '1986;': [3115], '869:': [3116], '275-285Crossref': [3117], 'progress': [3123], 'curves': [3124], 'show': [3132], 'levels': [3135], 'achieved': [3139], 'initial': [3143], 'velocities': [3144], 'proportional': [3146], 'logs.': [3152], 'ofT.': [3154], 'meets': [3161], 'criteria': [3163], 'use': [3166], 'transient-state': [3168], 'kinetics': [3169], 'calculate': [3171], 'inhibitors': [3177], '(50Cha': [3178], 'quasi-steady-state': [3201], '(3–30': [3203], 'NADPH,': [3208], 'μmH2-folate,': [3210], 'concentrations)': [3214], '(Equations': [3215], '6–9': [3216], 'Ref.': [3218], 'Lineweaver-Burk': [3231], 'plots': [3232, 3267, 3275], 'mode': [3238], 'pyrimethamine,': [3242], 'examining': [3243], 'ligand': [3244], 'competition': [3245], 'where': [3248], '[inhibitor]': [3249], '≪': [3250], '[enzyme]': [3251], '[H2-folate]': [3253], '0.5–10': [3255], 'm.': [3258], 'double-reciprocal': [3266], 'displayed': [3268], 'linearity,': [3269], 'supporting': [3270], 'conclusion': [3272], 'inappropriate': [3277], 'computation': [3279], 'ofK': [3280], 'structure': [3284, 3344, 3379], 'modeled': [3290], 'IRIS': [3293], 'Indigo': [3294], 'XZ4000': [3295], 'Homology': [3298], 'module': [3299], 'graphics': [3303], 'package': [3304], 'Insight': [3305, 3406], 'II': [3306, 3407], '(Biosym': [3307], 'Technologies).': [3308], 'structures': [3311], 'Leishmania': [3316], 'majorDHFR-TS': [3317], 'proteins': [3318], 'aligned': [3320], 'PAM250': [3323], 'matrix': [3324], 'identify': [3326], 'possible': [3327], 'conserved': [3328, 3381], 'regions.': [3329], 'Coordinates': [3330], 'assigned': [3332, 3384], 'residues': [3336], '2.9': [3339], 'Å': [3340], 'major': [3342], 'x-ray': [3343], '(generously': [3345], 'provided': [3346], 'Dr.': [3348], 'Matthews)': [3351], '(54Knight': [3352], 'D.R.': [3353], 'Kan': [3354], 'C.C.': [3355], 'Howland': [3356], 'Janson': [3358], 'C.A.': [3359], 'Hostomska': [3360], 'Welsh': [3362], 'Matthews': [3364], 'D.A.': [3365], 'Nat.': [3366], 'Struct.': [3367], '1:': [3370], '186-194Crossref': [3371], '(203)': [3374], 'loop': [3378], 'domains': [3382], 'root': [3386], 'mean': [3387], 'square': [3388], 'distance': [3389], 'minimization.': [3390], 'Energy': [3391], 'minimization': [3392], 'gondiienzyme': [3396], 'performed': [3401], 'convergence': [3403], 'Discover': [3408], 'module.': [3409], 'above,': [3412], 'there': [3413], 'strong': [3416], 'substitutions': [3430, 3746], "parasite's": [3433], 'subset': [3725], 'inP.': [3730], 'Table': [3736], 'I.': [3737], 'constructed': [3751], 'large': [3753], 'alleles,': [3760], 'including': [3761], 'analogous': [3763], 'strains': [3770], '(Table': [3771], 'II).': [3772], 'Mutagenesis': [3773], 'containingT.': [3781], 'junctional': [3785], 'sequence,': [3788], 'could': [3790], 'conveniently': [3793], 'insertion': [3798], 'encoding': [3806], '(Fig.': [3811], '1).Table': [3812], 'IDHFR-TS': [3813], 'falciparumPolymorphic': [3817], 'locusAmino': [3818], 'residueRef.Characteristics16Ala9Bzik': [3820], 'Scholar,16Peterson': [3842, 4035], 'ScholarMost': [3862, 4055, 4146], 'allele,': [3865], 'sensitive': [3866], 'cycloguanil.': [3870, 3907], 'Invariably': [3871], 'Ser-108.': [3874], 'Representive': [3875, 3912], 'isolate:': [3878, 3913], '3D7.Val16Peterson': [3879], 'ScholarRare': [3899, 4096], 'variant,': [3900], 'correlated': [3901], 'Always': [3908], 'Thr-108.': [3911], 'FCR3.59Ser9Bzik': [3914], 'ScholarWild-type': [3957], '(3D7,': [3958], 'FCR3).Arg15Cowman': [3959], 'ScholarOnly': [4004], 'association': [4007], '(K1).108Ser9Bzik': [4013], '(3D7).': [4059], 'Associated': [4060, 4099], 'Ala-16.': [4062], 'enzymes': [4067], 'contain': [4071], 'Thr': [4073], 'position.Thr16Peterson': [4076], 'variant': [4097], '(FCR3).': [4098], 'Val-16.Asn15Cowman': [4101], 'pyrimethamine-resistant': [4150], '(HB3).': [4152], 'Role': [4153], 'genetic': [4159], '(16Peterson': [4163], 'Sathit': [4239]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W1980479317', 'counts_by_year': [{'year': 2023, 'cited_by_count': 3}, {'year': 2022, 'cited_by_count': 1}, {'year': 2020, 'cited_by_count': 1}, {'year': 2019, 'cited_by_count': 4}, {'year': 2018, 'cited_by_count': 4}, {'year': 2017, 'cited_by_count': 1}, {'year': 2016, 'cited_by_count': 1}, {'year': 2015, 'cited_by_count': 1}, {'year': 2014, 'cited_by_count': 2}, {'year': 2013, 'cited_by_count': 3}], 'updated_date': '2024-12-18T10:26:54.648124', 'created_date': '2016-06-24'}