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1452, 1462, 1466, 1511, 1548, 1569, 1631, 1642, 1784, 1791, 1843, 1852, 1916, 1936, 1948, 2040, 2049, 2081, 2261, 2268, 2273, 2282, 2295, 2321, 2399, 2421, 2429, 2500, 2510, 2519, 2704, 2726, 2732, 2739, 2761, 2772, 2809, 2818, 2835, 2879, 2916, 2927, 2944, 2979, 2984, 2989, 3011, 3027, 3040, 3104, 3109, 3164, 3257, 3261, 3284, 3320, 3340, 3360, 3380, 3393, 3412, 3430, 3438, 3468, 3478, 3516, 3520, 3540, 3567, 3584, 3607, 3619, 3623, 3633, 3659, 3676, 3686, 3694, 3702, 3705, 3763, 3769, 3784, 3790, 3815, 3853, 3866, 3886, 3898, 3903, 3969, 4052, 4066, 4094, 4101, 4113, 4134, 4197, 4208, 4231, 4241, 4281, 4284, 4290, 4293, 4347, 4368, 4402, 4409, 4443, 4453, 4487, 4509, 4537, 4565, 4597, 4648, 4664, 4672], 'second': [10, 207, 4055], 'messenger': [11, 208, 416], 'cGMP': [12, 35, 92, 173, 209, 232, 289, 370, 412, 487, 533, 547, 569, 1005, 1024, 1096, 1786, 1839, 2416, 2707, 2838, 2852, 3096, 3123, 3281, 3585, 3634, 3785, 3795, 4315, 4638, 4657, 4681], 'in': [13, 75, 122, 210, 272, 319, 417, 472, 499, 899, 937, 1176, 1186, 1196, 1298, 1399, 1445, 1456, 1561, 1588, 1738, 1743, 1876, 1910, 1928, 1940, 1962, 1970, 2011, 2052, 2089, 2103, 2166, 2229, 2285, 2290, 2304, 2313, 2339, 2516, 2686, 2699, 2736, 2787, 2826, 2847, 2904, 2968, 2972, 3002, 3034, 3052, 3075, 3116, 3124, 3159, 3266, 3274, 3310, 3537, 3581, 3593, 3628, 3644, 3673, 3682, 3733, 3745, 3778, 3805, 3841, 3966, 4013, 4019, 4021, 4178, 4543, 4558, 4575, 4590, 4613, 4642, 4685], 'outer': [15, 212], 'segments': [16, 213], 'cone': [18, 67, 215, 264, 399, 607, 610, 645, 669, 692, 751, 1340, 3859], 'and': [19, 36, 109, 191, 216, 233, 306, 388, 398, 448, 484, 501, 618, 644, 668, 679, 681, 701, 772, 780, 812, 893, 935, 980, 988, 1039, 1192, 1267, 1308, 1315, 1364, 1502, 1533, 1586, 1625, 1647, 1711, 1741, 1769, 1778, 1794, 1814, 1868, 1884, 1931, 1938, 1958, 2096, 2100, 2152, 2234, 2270, 2280, 2327, 2350, 2367, 2411, 2455, 2482, 2529, 2589, 2606, 2642, 2702, 2747, 2799, 2804, 2824, 2845, 2856, 2885, 2987, 3058, 3069, 3094, 3157, 3199, 3353, 3365, 3397, 3434, 3501, 3544, 3561, 3573, 3614, 3631, 3712, 3727, 3860, 3871, 3877, 3929, 3936, 3939, 3956, 4031, 4041, 4132, 4199, 4210, 4217, 4286, 4305, 4355, 4399, 4418, 4451, 4466, 4499, 4525, 4580, 4625, 4644, 4650, 4658, 4666, 4674], 'rod': [20, 217, 397, 643, 667, 744, 1098, 1165, 3861, 4576], 'cells.': [22, 219], 'PDE6': [23, 42, 99, 189, 220, 239, 296, 386, 483, 536, 576, 648, 672, 693, 756, 993, 1099, 1170, 1280, 1321, 2324, 3854, 4463, 4577], 'contains': [24, 221, 673, 694, 2947, 3924, 4070, 4173, 4243], 'two': [25, 84, 222, 281, 674, 682, 695, 702, 2050, 2801, 2948, 2974, 3371, 3490, 3649, 3739, 4412], 'regulatory': [26, 223, 978], 'GAF': [27, 62, 104, 131, 149, 224, 259, 301, 328, 346, 776, 781, 795, 802, 837, 883, 986, 989, 996, 1190, 1273, 1292, 1335, 1351, 1362, 1366, 1375, 1442, 1454, 1458, 1513, 1550, 1871, 2325, 2332, 2514, 2684, 2756, 2765, 2778, 2930, 2934, 3014, 3048, 3061, 3088, 3105, 3111, 3126, 3162, 3201, 3250, 3271, 3578, 3626, 3640, 3678, 3707, 3792, 3855, 3900, 3916, 4067, 4096, 4104, 4118, 4126, 4233, 4239, 4295, 4391, 4444, 4517, 4520, 4523, 4527, 4670], 'domains,': [28, 225, 1352, 3251], 'which': [30, 82, 227, 279, 439, 1457, 1634, 2820, 2841, 3480, 3873, 3958, 4182], 'one': [31, 228, 758], '(GAF': [32, 229, 778], 'A)': [33, 230, 4528], 'binds': [34, 231, 447, 1175], 'activity': [39, 236, 943, 1266], 'holoenzyme.': [43, 240, 1322], 'To': [44, 241, 2713, 2997, 3751], 'increase': [45, 242, 1104, 3777], 'our': [46, 243], 'understanding': [47, 244], 'this': [49, 246, 581, 972, 1324], 'allosteric': [50, 247, 1032, 1312], 'regulation': [51, 185, 248, 382], 'mechanism,': [52, 249], 'we': [53, 250, 1286, 1326, 2521, 3004, 3290, 3598, 3755], 'present': [54, 251], '2.6Å': [56, 253], 'crystal': [57, 177, 254, 374, 1331, 1450, 2010, 2165, 2759, 2925, 2946, 3896], 'structure': [58, 170, 178, 255, 367, 375, 1332, 1440, 1451, 2760, 2926, 3809, 3817, 3897, 3918, 4230], 'cGMP-bound': [61, 258, 1529, 2431, 3012, 3059, 3615], 'A': [63, 105, 125, 132, 150, 260, 302, 322, 329, 347, 779, 987, 997, 1274, 1293, 1336, 1363, 1443, 1459, 1514, 1551, 1872, 1998, 2125, 2326, 2333, 2374, 2515, 2685, 2766, 2931, 2935, 3015, 3049, 3062, 3089, 3293, 3579, 3627, 3641, 3679, 3708, 3793, 3856, 3917, 4054, 4105, 4228, 4234, 4445, 4579], 'domain': [64, 106, 151, 261, 303, 348, 1029, 1202, 1294, 1337, 1873, 2779, 3272, 3580, 4106, 4127, 4240, 4446], 'chicken': [66, 263, 1296, 1339, 1537, 2763, 2928], 'PDE6.': [68, 265, 755, 1341], 'Nucleotide': [69, 266, 497], 'specificity': [70, 267, 3446], 'appears': [71, 268], 'to': [72, 87, 116, 181, 269, 284, 313, 378, 475, 559, 604, 614, 651, 686, 706, 787, 848, 1003, 1091, 1097, 1103, 1110, 1167, 1301, 1348, 1382, 1447, 1628, 1638, 1652, 1755, 1781, 1859, 1881, 1945, 2395, 2408, 2417, 2993, 3122, 3244, 3294, 3335, 3350, 3389, 3407, 3453, 3463, 3496, 3514, 3524, 3571, 3586, 3603, 3826, 3964, 4016, 4039, 4086, 4110, 4185, 4204, 4213, 4222, 4351, 4364, 4396, 4407, 4507, 4541, 4604], 'be': [73, 270, 652, 1092, 1860, 3965, 4035, 4043, 4087, 4433, 4468], 'provided': [74, 271, 2303, 3473], 'part': [76, 273, 1461], 'by': [77, 274, 396, 552, 1233, 1863, 2092, 2625, 2889, 2961, 3020, 3420, 3474, 3665, 3723, 3933, 4435], 'orientation': [79, 276, 2971], 'Asn-116,': [81, 278, 4187, 4397], 'makes': [83, 280, 3347, 3384, 3401, 4599, 4626], 'hydrogen': [85, 282, 3375, 3387, 3405, 3451, 3461, 3492, 3512, 3528, 4202, 4226, 4361, 4387, 4414, 4430, 4490, 4602, 4621, 4629], 'bonds': [86, 283, 3493, 4203, 4415, 4431], 'guanine': [89, 286, 3345, 3395, 3470, 3518, 3548, 4353, 4376, 4382, 4511, 4562, 4606], 'ring': [90, 287, 3346, 3471, 3504, 3519, 3549], 'but': [93, 154, 290, 351, 1022, 1707, 1823, 3589, 4683], 'is': [94, 107, 152, 291, 304, 349, 404, 570, 577, 747, 757, 796, 1346, 1390, 1460, 1523, 2821, 2842, 2967, 3033, 3050, 3090, 3114, 3264, 3273, 3309, 3354, 3416, 3472, 3481, 3550, 3642, 3663, 4060, 4083, 4107, 4129, 4183, 4349, 4359, 4372, 4459, 4494, 4539, 4556, 4582, 4587, 4615], 'not': [95, 111, 292, 308, 2937, 2952, 3099, 3742, 3824], 'strictly': [96, 293, 3887], 'conserved': [97, 127, 294, 324, 790, 886, 3881, 3888, 3905, 4010, 4057], 'among': [98, 295, 3688], 'isoforms.': [100, 297, 670], 'isolated': [102, 299], 'PDE6C': [103, 300, 999, 1297, 1361, 1512, 1538, 2331, 2513, 2683, 2764, 2929, 3060, 3110, 3577, 3625, 3639, 3706, 3791, 3899, 3915, 4103, 4285, 4390, 4538, 4566, 4592, 4598, 4643], 'monomeric': [108, 305, 1439, 3000, 3051], 'does': [110, 307, 2936, 3098, 3823], 'contain': [112, 309, 774], 'sufficient': [113, 310], 'structural': [114, 159, 311, 356, 1306, 1520, 2300, 3748], 'determinants': [115, 312, 654], 'form': [117, 314, 687, 707, 1510, 2866, 2938, 3907], 'a': [118, 134, 156, 162, 315, 331, 353, 359, 405, 565, 599, 688, 1328, 1353, 1378, 1467, 1516, 1540, 1639, 1744, 1756, 2009, 2104, 2155, 2164, 2370, 2396, 2418, 2442, 2572, 2671, 2730, 2748, 2770, 2776, 2782, 2810, 2867, 2895, 2911, 2939, 2969, 2980, 2990, 3035, 3092, 3275, 3285, 3358, 3385, 3402, 3421, 3449, 3668, 3692, 3715, 3767, 3883, 3908, 4174, 4188, 4244, 4360, 4385, 4422, 4440, 4474, 4583, 4588, 4600, 4619, 4627, 4661], 'homodimer': [119, 316], 'as': [120, 317, 413, 659, 895, 1035, 1231, 1396, 1705, 1819, 2358, 2729, 3655, 3766, 3832, 4138, 4421, 4428, 4489, 4554], 'found': [121, 318, 2087], 'full-length': [123, 320, 1536], 'PDE6C.': [124, 321], 'highly': [126, 323], 'surface': [128, 325, 3259, 3911, 3922, 3943, 4011, 4026, 4058, 4090], 'patch': [129, 326, 3912, 3923, 4059], 'on': [130, 327, 2441, 2571, 2670, 2875, 3913, 4062], 'indicates': [133, 330, 2932, 3786], 'potential': [135, 332], 'binding': [136, 333, 842, 1025, 1106, 1185, 1263, 3097, 3297, 4291, 4427, 4682], 'site': [137, 334, 1314, 3972], 'for': [138, 335, 572, 580, 1037, 1275, 1535, 1597, 1655, 1967, 2047, 2098, 2334, 2426, 2619, 3025, 3038, 3718, 4045, 4091, 4309, 4314, 4618, 4680], 'inhibitory': [140, 337, 451, 683], 'subunit': [141, 338, 446, 452, 481, 662], 'Pγ.': [142, 339, 4053, 4092], 'NMR': [143, 340, 1234, 1501, 2328, 2335, 2404, 3601], 'studies': [144, 341, 736, 1163, 1505, 2336, 2667], 'reveal': [145, 342, 1506], 'that': [146, 343, 410, 664, 783, 844, 1173, 1372, 1389, 1507, 1522, 2870, 2893, 2933, 2950, 3047, 3087, 3095, 3269, 3278, 3304, 3638, 3737, 3801, 3864, 4081, 4236, 4298, 4457, 4496], 'apo-PDE6C': [148, 345, 3677], 'structured': [153, 350], 'adopts': [155, 352, 1515], 'significantly': [157, 354, 1524, 3652, 3744], 'altered': [158, 355, 1525, 3829], 'state': [160, 357, 1521, 3001, 3103, 3277], 'indicating': [161, 358, 1371, 3268, 4080], 'large': [163, 360, 3884], 'conformational': [164, 361, 1033, 3609, 3821], 'change': [165, 362, 1034, 3610, 3822], 'with': [166, 363, 434, 1180, 1392, 1527, 1767, 1775, 1796, 1824, 1832, 1913, 2057, 2174, 2264, 2343, 2379, 2448, 2680, 2742, 2781, 2864, 2910, 2954, 2958, 3691, 3882, 4027, 4048, 4374, 4560, 4636, 4660], 'rearrangement': [167, 364], 'secondary': [169, 366, 3720, 3747, 3816], 'elements': [171, 368], 'upon': [172, 369, 3280, 3565, 3782], 'binding.': [174, 196, 371, 393, 3282, 3796], 'presented': [176, 373], 'will': [179, 376], 'help': [180, 377, 4212], 'define': [182, 379], 'cGMP-dependent': [184, 381], 'mechanism': [186, 383], 'holoenzyme': [190, 387, 742, 1112, 1281], 'its': [192, 389, 3381, 3398, 3431, 4215, 4356], 'inhibition': [193, 390], 'through': [194, 391, 554, 1030, 2718, 3016, 3357, 3448, 3794, 3812], 'Pγ': [195, 392, 453, 684, 704, 1109, 1166, 1174, 1262], 'Light': [394, 2035], 'detection': [395, 901], 'photoreceptors': [400, 595, 611, 3862], 'vertebrate': [402, 761], 'retina': [403], 'complex': [406], 'signal': [407, 622, 896, 1400, 2725, 3717, 3762], 'transduction': [408, 897, 1401], 'process': [409], 'utilizes': [411], 'an': [414, 424, 450, 1031, 1177, 1299, 1387, 1629, 2265, 2890, 3508, 3534, 3656, 3827, 4469, 4471, 4530], 'conversion': [419], 'photon': [421], 'stimulation': [422], 'into': [423, 1304, 1886, 3418, 4220], 'electrical': [425], 'response.': [426], 'Upon': [427, 2392], 'light': [428, 605, 621, 900], 'stimulation,': [429], 'phototransduction': [431], 'cascade': [432], 'begins': [433], 'activation': [435, 477], 'light-sensitive': [437], 'rhodopsin,': [438], 'activates': [440, 1026], 'G-protein': [442], 'transducin,': [443], 'whose': [444], 'Gα': [445], 'sequesters': [449], '(PDE6).': [458], '4The': [459], 'abbreviations': [460], 'used': [461, 2097, 2618], 'are:': [462], 'PDE6photoreceptor': [463], 'phosphodiesterasePDE3′,': [464], '5′-cyclic': [465, 586], 'nucleotide': [466, 587, 763, 3263, 3545], 'phosphodiesteraseHSQCheteronuclear': [467], 'single': [468, 590, 2375], 'quantum': [469, 591], 'correlationSeMetselenomethionine.': [470], 'This': [471, 3485, 3797, 3921, 4171], 'turn': [473, 4177, 4247], 'leads': [474], 'catalytic': [480, 676, 698, 791, 1028, 1169, 1201, 1265], 'hydrolysis': [485], '(1Cote': [488], 'R.H.': [489, 1114], 'Beavo': [490, 853, 1008, 1045, 1482, 3140, 3180, 4152, 4260, 4326, 4701], 'J.A.': [491, 854, 1009, 1046, 1483, 3141, 3181, 4153, 4261, 4327, 4702], 'Francis': [492, 871, 1078], 'S.H.': [493, 872, 1079], 'Houslay': [494], 'M.D.': [495, 1116], 'Cyclic': [496], 'Phosphodiesterases': [498], 'Health': [500], 'Disease.': [502], 'CRC': [503], 'Press,': [504], 'Inc.,': [505], 'Boca': [506], 'Raton,': [507], 'FL2007:': [508], '165-193Google': [509], 'Scholar,': [510, 866, 1058, 1133, 1420, 3988], '2Arshavsky': [511], 'V.Y.': [512, 1118], 'Lamb': [513], 'T.D.': [514], 'Pugh': [515], 'Jr.,': [516, 626], 'E.N.': [517, 627], 'Annu': [518], 'Rev.': [519], 'Physiol.': [520], '2002;': [521, 859, 1149, 1491, 3149, 3998], '64:': [522, 928], '153-187Crossref': [523], 'PubMed': [524, 635, 728, 832, 862, 878, 916, 930, 966, 1019, 1056, 1085, 1129, 1157, 1226, 1257, 1416, 1433, 1494, 1581, 1617, 2074, 2120, 2147, 2220, 2252, 2477, 2494, 2563, 2637, 2658, 3152, 3194, 3238, 3984, 4001, 4166, 4275, 4339], 'Scopus': [525, 636, 729, 833, 863, 879, 917, 931, 967, 1086, 1130, 1158, 1227, 1258, 1417, 1434, 1495, 1582, 1618, 2075, 2121, 2148, 2221, 2253, 2478, 2495, 2564, 2638, 2659, 3153, 3195, 3239, 3985, 4002, 4167, 4276, 4340], '(506)': [526], 'Google': [527, 638, 731, 835, 865, 881, 919, 933, 969, 1020, 1057, 1088, 1132, 1160, 1229, 1260, 1419, 1436, 1497, 1584, 1620, 2077, 2123, 2150, 2223, 2255, 2480, 2497, 2566, 2640, 2661, 3155, 3197, 3241, 3987, 4004, 4169, 4278, 4342], 'Scholar).': [528, 639, 732, 836, 882, 970, 1161, 1261, 1437, 1498, 2078, 2124, 2224, 2256, 2498, 2662, 3242, 4170, 4279, 4343], 'By': [529], 'lowering': [530], 'levels,': [534], 'activated': [535], 'causes': [537], 'hyperpolarization': [538], 'cell': [542], 'via': [543, 4384], 'cGMP-gated': [544], 'ion': [545], 'channels.': [546], 'are': [549, 596, 612, 649, 784, 839, 845, 885, 2302, 2311, 2887, 3569, 3709, 3879, 3931, 4006, 4640], 'quickly': [550, 617], 'restored': [551], 'synthesis': [553], 'calcium-sensitive': [555], 'guanylyl': [557], 'cyclases': [558], 're-establish': [560], 'dark-adapted': [562], 'state.': [563, 1530], 'As': [564, 1277, 4478], 'rapid': [566], 'turnover': [567], 'mandatory': [571], 'effective': [573], 'visual': [574], 'function,': [575], 'well': [578, 2614, 2909, 3355], 'adapted': [579], 'purpose.': [582], '3′,': [585], 'heteronuclear': [589, 2532], 'correlation': [592, 2508, 3008], 'selenomethionine.': [593], 'Rod': [594, 671], 'at': [597, 1622, 1633, 1661, 1731, 1746, 1907, 2019, 2031, 2438, 2568, 2722, 2752, 2769, 3030, 3054, 3064, 3725, 3759, 4532], 'least': [598], 'hundred': [600], 'times': [601], 'more': [602, 616, 623, 789, 888, 3666], 'sensitive': [603], 'than': [606, 889, 3667, 3811], 'photoreceptors.': [608, 745], 'Nevertheless,': [609, 3819], 'able': [613, 3570], 'respond': [615], 'terminate': [619], 'rapidly': [624], '(3Pugh': [625], 'Cobbs': [628], 'W.H.': [629], 'Vision': [630, 3979], 'Res.': [631, 3980], '1986;': [632], '26:': [633], '1613-1643Crossref': [634], '(122)': [637], 'Structural': [640, 4646], 'differences': [641], 'between': [642, 666, 2822, 2843, 3425, 3552, 3611, 3869, 4123], 'isoforms': [646], 'thought': [650], 'critical': [653, 4189], 'responses': [658], 'they': [660], 'display': [661, 941], 'organizations': [663], 'differ': [665, 3743, 3804], 'distinct': [675, 2981], 'subunits': [677, 685, 699, 705], '(α': [678], 'β)': [680], 'heterotetramer': [689], '(Pαβγ2),': [690], 'whereas': [691, 4378, 4585, 4608], 'identical': [696, 1385, 3071], 'cone-specific': [697, 703], 'α′': [700], 'Pα′2γ2': [708], '(4Artemyev': [709], 'N.O.': [710, 1212, 1242, 3978, 3996], 'Surendran': [711], 'R.': [712, 868, 2542, 3216], 'Lee': [713], 'J.C.': [714], 'Hamm': [715], 'H.E.': [716], 'J.': [717, 1010, 1047, 1077, 1146, 1215, 1236, 1427, 1575, 1610, 1611, 2064, 2198, 2468, 2471, 2488, 2631, 2652, 3220, 3227, 4264, 4328, 4703], 'Biol.': [718, 1011, 1048, 1147, 1216, 1429, 1577, 1613, 2069, 2115, 2142, 2215, 2247, 2654, 3228, 4265, 4329, 4704], 'Chem.': [719, 1012, 1049, 1148, 1217, 3229, 4266, 4330, 4705], '1996;': [720, 1578], '271:': [721], '25382-25388Abstract': [722], 'Full': [723, 725, 829, 1016, 1053, 1152, 1154, 1221, 1223, 1413, 3233, 3235, 4270, 4272, 4334, 4336], 'Text': [724, 726, 830, 1017, 1054, 1153, 1155, 1222, 1224, 1414, 3234, 3236, 4271, 4273, 4335, 4337], 'PDF': [727, 831, 1018, 1055, 1156, 1225, 1415, 3237, 4274, 4338], '(29)': [730], 'Most': [733], 'previous': [734], 'biochemical': [735], 'have': [737, 1287, 1377, 3070, 3590, 3714, 3960, 4483, 4529, 4676], 'utilized': [738, 1288, 3599], 'heteromeric': [740], 'Pαβγ2': [741], 'from': [743, 798, 998, 1338, 1543, 1849, 2008, 2163, 3556, 3858, 4037, 4448, 4653, 4690], 'Less': [746], 'known': [748, 1350], 'about': [749], 'isoform': [753], '11': [760], 'cyclic': [762, 3248, 4116], 'PDE': [764, 1374], 'families.': [765], 'Of': [766], 'these,': [767], 'PDE2,': [768], '-5,': [769], '-6,': [770], '-10,': [771], '-11': [773], 'tandem': [775, 3161, 4669], 'domains': [777, 838, 843, 850, 884, 991, 1376, 1398, 3163, 4518, 4652, 4671], 'B)': [782, 4581], 'located': [785, 4061], 'N-terminally': [786], 'domains.': [792, 4119], 'acronym': [794], 'derived': [797], 'first': [800, 2860], 'identified': [801], 'domain-containing': [803], 'protein': [804, 1599, 1829, 1845, 1856, 1937, 3352, 3753], 'families:': [805], 'mammalian': [806], 'cGMP-regulated': [807], 'PDEs,': [808], 'Anabaena': [809], 'adenylyl': [810, 3167], 'cyclases,': [811], 'Escherichia': [814], 'coli': [815, 1564], 'transcription': [816], 'factor': [817, 2267, 2272], 'FhlA': [818], '(5Aravind': [819, 1403], 'L.': [820, 1404, 1426], 'Ponting': [821, 1405], 'C.P.': [822, 1406], 'Trends': [823, 1407], 'Biochem.': [824, 1408], 'Sci.': [825, 959, 1122, 1250, 1409, 1487, 3145, 3187, 4159], '1997;': [826, 1410, 2249], '22:': [827, 1411], '458-459Abstract': [828, 1412], '(490)': [834, 1418], 'small': [840], 'molecule': [841, 4639], 'structurally': [846], 'related': [847, 2088, 2960], 'Per-ARNT-Sim': [849], '(6Martinez': [851], 'S.E.': [852, 1471, 2552, 3129, 3171, 4143, 4323, 4698], 'Hol': [855, 1480, 3138], 'W.G.': [856, 1481, 3139], 'Mol.': [857, 873, 925, 1080, 1428, 1576, 1612, 2653], 'Interv.': [858], '2:': [860], '317-323Crossref': [861], '(111)': [864], '7Zoraghi': [867], 'Corbin': [869], 'J.D.': [870, 1060, 2556], 'Pharmacol.': [874, 1081], '2004;': [875, 2144, 3981, 4331, 4706], '65:': [876], '267-278Crossref': [877], '(125)': [880], 'over': [887, 2919, 4316], '3': [890, 2745], 'billion': [891], 'years': [892], 'function': [894, 1309, 2731, 3768], 'modules': [898], 'plants': [903], '(8Wagner': [904], 'J.R.': [905, 4251], 'Brunzelle': [906], 'J.S.': [907, 2196], 'Forest': [908], 'K.T.': [909], 'Vierstra': [910], 'R.D.': [911], 'Nature.': [912], '2005;': [913, 3191, 4163], '438:': [914], '325-331Crossref': [915], '(441)': [918], 'Scholar),': [920, 934, 1021, 4005], 'sodium': [921, 1924, 1983, 2385, 2692], 'sensing': [922], '(9Cann': [923], 'M.': [924, 1135, 2200, 2648, 3210, 3224], 'Microbiol.': [926], '2007;': [927, 963], '461-472Crossref': [929], '(26)': [932, 1159], 'may': [936, 3442, 4042, 4211], 'some': [938], 'cases': [939], 'even': [940], 'enzymatic': [942], '(10Lin': [944], 'Z.': [945], 'Johnson': [946], 'L.C.': [947], 'Weissbach': [948], 'H.': [949, 1206, 1240, 3974], 'Brot': [950], 'N.': [951, 1137, 3177, 3204, 4149], 'Lively': [952], 'M.O.': [953], 'Lowther': [954], 'W.T.': [955], 'Proc.': [956, 1119, 1247, 1484, 3142, 3184, 4156], 'Natl.': [957, 1120, 1248, 1485, 3143, 3185, 4157], 'Acad.': [958, 1121, 1249, 1486, 3144, 3186, 4158], 'U.': [960, 1123, 1251, 1488, 3146, 3188, 4160], 'S.': [961, 1124, 1252, 1479, 1489, 2462, 3137, 3147, 3173, 3189, 3208, 3212, 3226, 4145, 4161], 'A.': [962, 1067, 1125, 1145, 1253, 1490, 2470, 3106, 3148, 3175, 3190, 4068, 4147, 4162], '104:': [964], '9597-9602Crossref': [965], '(116)': [968], 'At': [971], 'point,': [973], 'details': [975], 'mechanism(s)': [979], 'exact': [982], 'roles': [983], 'B': [990, 1367, 2181, 3127, 3202, 3288, 4296], 'remain': [994], 'elusive.': [995], 'has': [1000, 1100, 1282], 'been': [1001, 1101, 1283, 3591, 3961], 'shown': [1002, 1102], 'bind': [1004, 1383, 4656], '(11Gillespie': [1006], 'P.G.': [1007], '1988;': [1013], '263:': [1014], '8133-8141Abstract': [1015], 'whether': [1023], 'reported': [1036], 'PDE2A': [1038, 1365, 1453, 3125, 4294, 4673], 'PDE5A': [1040, 4232, 4242, 4522, 4675], '(12Martins': [1041], 'T.J.': [1042], 'Mumby': [1043], 'M.C.': [1044], '1982;': [1050], '257:': [1051], '1973-1979Abstract': [1052], '13Corbin': [1059], 'Blount': [1061], 'M.A.': [1062], 'Weeks': [1063], '2nd,': [1064], 'J.L.': [1065, 1246], 'Beasley': [1066], 'Kuhn': [1068], 'K.P.': [1069], 'Ho': [1070], 'Y.S.': [1071], 'Saidi': [1072], 'L.F.': [1073], 'Hurley': [1074], 'J.H.': [1075], 'Kotera': [1076, 3219], '2003;': [1082], '63:': [1083], '1364-1372Crossref': [1084], '(64)': [1087], 'Scholar)': [1089, 1230, 1621, 2151, 2481, 2567, 2641, 3156, 3198], 'remains': [1090], 'determined.': [1093], 'Binding': [1094, 3566], 'affinity': [1107, 1271, 1787, 2352, 4313], '(14Cote': [1113], 'Bownds': [1115], 'Arshavsky': [1117], '1994;': [1126, 2491, 2560, 2634], '91:': [1127], '4845-4849Crossref': [1128], '(85)': [1131], '15Yamazaki': [1134], 'Li': [1136], 'Bondarenko': [1138], 'V.A.': [1139], 'Yamazaki': [1140, 1144], 'R.K.': [1141], 'Baehr': [1142], 'W.': [1143], '277:': [1150], '40675-40686Abstract': [1151], 'Cross-linking': [1162], 'αβ-heterodimer': [1171], 'revealed': [1172, 4235, 4297], 'extended': [1178], 'manner,': [1179], 'N-terminal,': [1182], 'polycationic': [1183, 4050], 'region': [1184, 1195, 4051], 'vicinity': [1188, 1198, 3968], 'A,': [1191, 3901, 4392, 4524], 'C-terminal': [1194, 1556], '(16Guo': [1203], 'L.W.': [1204, 1238], 'Muradov': [1205, 1239], 'Hajipour': [1207], 'A.R.': [1208], 'Sievert': [1209], 'M.K.': [1210], 'Artemyev': [1211, 1241, 3977, 3995], 'Ruoho': [1213, 1243], 'A.E.': [1214, 1244, 3992], '2006;': [1218], '281:': [1219], '15412-15422Abstract': [1220], '(42)': [1228], 'confirmed': [1232], '(17Song': [1235], 'Guo': [1237], 'Markley': [1245], '2008;': [1254, 3230, 4267], '105:': [1255], '1505-1510Crossref': [1256], '(79)': [1259], 'blocks': [1264], 'also': [1268, 3488, 4007], 'increases': [1269], 'cGMP.': [1276, 1903, 3413, 3521], 'no': [1278, 3838], 'recombinant': [1279, 3576], 'successfully': [1284], 'expressed,': [1285], 'recombinantly': [1290], 'expressed': [1291, 1560], 'attempt': [1300], 'gain': [1302], 'insights': [1303], 'nature': [1307, 3606], 'cGMP-binding': [1313, 1358, 2813, 2881, 3107, 3542, 4282, 4516], 'oligomerization': [1318], 'In': [1323, 3522, 4192, 4389], 'study,': [1325], 'report': [1327], '2.6': [1329, 2156, 2773], 'Å': [1330, 2000, 2106, 2157, 2918, 3404, 3483, 3511], 'Although': [1342], 'overall': [1344, 3287, 3828, 4099], 'fold': [1345, 2780, 4100], 'similar': [1347, 3041, 3121, 4109, 4245, 4503, 4641], 'other': [1349, 2956, 4514], 'detailed': [1354], 'comparison': [1355], 'pockets': [1359], 'reveals': [1368, 3637, 3837, 3863, 4456], 'significant': [1369], 'differences,': [1370], 'variety': [1379, 4663], 'ways': [1381], 'ligand,': [1386], 'observation': [1388], 'consistent': [1391], 'their': [1393, 3683, 3746, 3806, 4686], 'widespread': [1394], 'occurrence': [1395], 'ligand-binding': [1397], 'pathways': [1402], '18Anantharaman': [1421], 'V.': [1422], 'Koonin': [1423], 'E.V.': [1424], 'Aravind': [1425], '2001;': [1430], '307:': [1431], '1271-1292Crossref': [1432], '(218)': [1435], 'stands': [1444], 'contrast': [1446], 'dimeric': [1449], 'AB,': [1455], 'dimerization': [1464, 2991], 'interface': [1465, 2992], 'parallel': [1468, 4559], 'dimer': [1469], '(19Martinez': [1470, 3128], 'Wu': [1472, 3130], 'A.Y.': [1473, 3131, 4319, 4694], 'Glavas': [1474, 3132], 'N.A.': [1475, 2540, 3133], 'Tang': [1476, 3134, 4320, 4695], 'X.B.': [1477, 3135, 4321, 4696], 'Turley': [1478, 3136], '99:': [1492, 3150], '13260-13265Crossref': [1493, 3151], '(226)': [1496, 3154], 'Furthermore,': [1499, 3414], 'combined': [1500], 'circular': [1503], 'dichroism': [1504, 2666, 3700], 'ligand-free': [1509, 3613], 'thermodynamically': [1517], 'less': [1518, 4084], 'stable': [1519], 'compared': [1526], 'Cloning,': [1531], 'Expression,': [1532], 'Purification—cDNA': [1534], 'was': [1539, 1559, 1645, 1650, 1659, 1753, 1765, 1773, 1830, 1857, 1874, 2006, 2127, 2227, 2278, 2337, 2365, 2377, 2402, 2414, 2424, 2734, 4139], 'generous': [1541], 'gift': [1542], 'Dr.': [1544], 'Susan': [1545], 'Semple-Rowland': [1546], '(University': [1547], 'Florida).': [1549], '(residues': [1552], '55–225': [1553, 2263], 'plus': [1554, 1595], 'LE(H6)': [1557], 'tag)': [1558], 'C41': [1562], 'E.': [1563, 3206], 'cells': [1565, 1735], '(a': [1566], 'derivative': [1567], 'strain': [1568], 'BL21(DE3)': [1570], '(20Miroux': [1571], 'B.': [1572], 'Walker': [1573], 'J.E.': [1574, 3179, 4151], '260:': [1579], '289-298Crossref': [1580], '(1586)': [1583], 'Scholar))': [1585], 'grown': [1587, 1906, 2338], 'LB': [1589, 1853], 'media': [1590, 1594, 2342], 'or': [1591, 1976, 1987, 2957, 3844, 4012, 4473], 'M9': [1592, 2340], 'minimal': [1593, 2341], 'Se-Met': [1596, 2003], 'Se-Met-labeled': [1598], '(21Van': [1600], 'Duyne': [1601], 'G.D.': [1602], 'Standaert': [1603], 'R.F.': [1604], 'Karplus': [1605], 'P.A.': [1606], 'Schreiber': [1607], 'S.L.': [1608], 'Clardy': [1609], '1993;': [1614], '229:': [1615], '105-124Crossref': [1616], '(1091)': [1619], '37': [1623, 2569, 3031], '°C': [1624, 1654, 2440, 2570, 2741, 2746, 3032, 3776], '200': [1626], 'rpm': [1627], 'A600': [1630], '∼0.5–0.6,': [1632], 'point': [1635], 'isopropyl': [1636], '1-thio-β-d-galactopyranoside': [1637], 'final': [1640, 2258, 2287, 2397, 2419], 'concentration': [1641, 2398, 2420], '0.2': [1643, 1825], 'mm': [1644, 1670, 1675, 1678, 1683, 1688, 1693, 1698, 1701, 1709, 1714, 1719, 1724, 1727, 1804, 1809, 1812, 1838, 1888, 1893, 1896, 1899, 1902, 1982, 1990, 1993, 1996, 2381, 2384, 2390, 2401, 2423, 2512, 2688, 2691, 2697, 2706], 'added,': [1646], 'temperature': [1649, 1909, 2733, 3770, 3781], 'lowered': [1651], '16': [1653], '18–24': [1656], 'h.': [1657], 'Purification': [1658], 'performed': [1660, 2228, 2669], '4': [1662], '°C.': [1663], 'Four': [1664], 'buffers': [1665], 'were': [1666, 1736, 1846, 1905, 1959, 2055, 2086, 2289, 2355, 2406, 2436, 2453, 2581, 2594, 2599, 2611, 2617, 2668, 2678, 4307], 'prepared:': [1667], 'lysis': [1668, 1739, 2349], '(50': [1669, 1687, 1713], 'Tris-HCl,': [1671, 1689, 1715, 1805, 1889], 'pH': [1672, 1690, 1716, 1806, 1890, 1926, 1985, 2387, 2694], '8.0,': [1673, 1691, 1717], '50': [1674], 'NaCl,': [1676, 1699, 1725, 1802, 1894, 2382, 2689], '5': [1677, 1882], 'imidazole,': [1679, 1694, 1720], '20%': [1680, 1695, 1721], 'glycerol,': [1681, 1696, 1722, 1974], '1': [1682, 1811, 1837, 1898, 1901, 1989, 1992, 2400, 2422], 'phenylmethylsulfonyl': [1684], 'fluoride);': [1685], 'wash-1': [1686, 1768], '15': [1692], '400': [1697], '2': [1700, 1726], 'MgCl2);': [1702], 'wash-2': [1703, 1770], '(same': [1704, 1818], 'wash-1,': [1706], '10': [1708, 1723, 2042], 'NaCl);': [1710], 'elution': [1712, 1776, 3067, 3072], '250': [1718, 1953], 'MgCl2).': [1728], 'After': [1729, 1749], 'centrifugation': [1730], '3,000': [1732], '×': [1733, 1950, 1952, 2028], 'g,': [1734], 'resuspended': [1737], 'buffer': [1740, 1777, 1799, 1817, 1822, 1835], 'lysed': [1742], 'microfluidizer': [1745], '10,000': [1747], 'p.s.i.': [1748], 'centrifugation,': [1750], 'lysate': [1752], 'applied': [1754, 1780], 'nickel-nitrilotriacetic': [1757], 'acid': [1758, 4574], 'gravity': [1759], 'column': [1760, 1764, 2353, 2363], '(15': [1761], 'ml).': [1762], 'washed': [1766, 1795], 'buffers.': [1771], 'Protein': [1772, 2315], 'eluted': [1774, 1831, 2378], 'then': [1779, 1960], '25': [1782, 1792, 2383, 2690], 'ml': [1783, 1915], 'epoxy-Sepharose': [1785], 'resin': [1788], '(column': [1789], 'size': [1790, 3042, 3077, 3834], 'mm)': [1793], 'high': [1797, 1820], 'salt': [1798, 1816, 1821, 1834, 3423], '(0.5': [1800], 'm': [1801, 1826, 1919, 1923, 1978, 2016, 2171], '20': [1803, 1887, 1892, 2439, 3775], '7.5,': [1807, 1891], '0.1': [1808, 1895, 1922, 1995, 2389, 2696, 2711], 'EDTA,': [1810, 1897], 'β-mercaptoethanol)': [1813], 'low': [1815, 1833, 4677], 'NaCl).': [1827], '(plus': [1836], '(Sigma)).': [1840], 'Usual': [1841], 'yields': [1842], 'purified': [1844, 1870], '∼5': [1847], 'mg': [1848], '9': [1850], 'liters': [1851], 'culture.': [1854], 'determined': [1858, 2056, 2768, 3005], '>95%': [1861], 'pure': [1862], 'SDS-PAGE.': [1864], 'Crystallization,': [1865], 'Structure': [1866], 'Determination,': [1867], 'Refinement—The': [1869], 'concentrated': [1875, 2366, 2407], 'Centricon': [1877], '30': [1878], 'units': [1879], '(Millipore)': [1880], 'mg/ml': [1883], 'exchanged': [1885], 'β-mercaptoethanol,': [1900, 1994], 'Crystals': [1904, 1943], 'room': [1908], 'sitting': [1911], 'drops': [1912], '0.5': [1914, 2705, 2917], 'precipitant': [1917, 1939], '(1.5–1.8': [1918], 'ammonium': [1920, 1979, 2017, 2172], 'sulfate,': [1921, 1980], 'acetate,': [1925, 1984], '4.5–5.0)': [1927], 'reservoir': [1930], 'equal': [1932], 'volumes': [1933], '(2–10': [1934], 'μl)': [1935], 'drop.': [1942], 'grew': [1944], 'maximum': [1946], 'dimensions': [1947], '∼600': [1949], '300': [1951], 'μm': [1954, 2682], 'within': [1955, 4008, 4461], 'several': [1956, 3348, 3902, 3925, 4071], 'weeks': [1957], 'frozen': [1961], 'liquid': [1963], 'nitrogen': [1964], 'after': [1965], 'soaking': [1966], '2–3': [1968], 'min': [1969], 'cryo-buffer': [1971, 2012, 2167], '(20%': [1972], 'v/v': [1973], '1.5': [1975, 2170], '1.6': [1977, 2015], '100': [1981, 2687], '4.5': [1986], '5.0,': [1988, 2014], 'cGMP,': [1991, 2520], 'EDTA).': [1997], '2.5': [1999], 'SAD': [2001], 'peak': [2002, 2376, 3073, 3842], 'data': [2004, 2160, 3085], 'set': [2005, 2161], 'collected': [2007, 2162, 2437, 2679], '(pH': [2013, 2168], 'sulfate)': [2018, 2173], '12,662.5': [2020], 'eV': [2021, 2025], '(0.97912': [2022], 'Å)': [2023, 4624], '(1': [2024], '=': [2026], '1.602': [2027], '10–19': [2029], 'J)': [2030], 'National': [2033], 'Synchrotron': [2034], 'Source': [2036], 'beamline': [2037], 'X4A.': [2038], 'Nine': [2039], 'selenium': [2043, 2083], 'atoms': [2044, 4485], '(five': [2045], 'seleniums': [2046], 'each': [2048, 2085, 2753, 2955, 2985, 4501], 'monomers': [2051, 2903, 2949, 2959, 2975], 'asymmetric': [2053, 2906, 2942], 'unit)': [2054], 'program': [2059, 2133, 2176], 'SOLVE': [2060], '(22Terwilliger': [2061], 'T.C.': [2062, 2110], 'Berendzen': [2063], 'Acta': [2065, 2111, 2138, 2211, 2243], 'Crystallogr.': [2066, 2070, 2112, 2116, 2139, 2143, 2212, 2216, 2244, 2248], 'Sect.': [2067, 2113, 2140, 2213, 2245], 'D': [2068, 2114, 2141, 2214, 2246], '1999;': [2071], '55:': [2072], '849-861Crossref': [2073], '(3219)': [2076], 'Two': [2079], 'sets': [2080], 'four': [2082], 'positions': [2084], 'density': [2091, 3301], 'non-point': [2093], 'group': [2094, 2277, 2834, 3308, 3333, 3437, 3457, 3467, 3500], 'symmetry': [2095], 'averaging': [2099], 'solvent': [2101], 'flattening': [2102], '3.0': [2105], 'RESOLVE': [2107], 'map': [2108, 3302], '(23Terwilliger': [2109], '2000;': [2117], '56:': [2118], '965-972Crossref': [2119], '(1635)': [2122], 'model': [2126, 2259, 2288], 'built': [2128], 'manually': [2129], 'using': [2130, 2154, 2178, 2231, 2457, 2535], 'COOT': [2132], '(24Emsley': [2134], 'P.': [2135, 2192, 4257], 'Cowtan': [2136], 'K.': [2137, 3218, 4325, 4700], '60:': [2145], '2126-2132Crossref': [2146], '(23605)': [2149], 'refined': [2153], 'native': [2158], 'sulfomethionine': [2159], '4.5,': [2169], 'CNS,': [2177], 'restrained': [2179], 'individual': [2180], 'factors': [2182], '(25Brunger': [2183], 'A.T.': [2184], 'Adams': [2185], 'P.D.': [2186], 'Clore': [2187], 'G.M.': [2188], 'DeLano': [2189], 'W.L.': [2190], 'Gros': [2191], 'Grosse-Kunstleve': [2193], 'R.W.': [2194], 'Jiang': [2195], 'Kuszewski': [2197], 'Nilges': [2199], 'Pannu': [2201], 'N.S.': [2202], 'Read': [2203], 'R.J.': [2204], 'Rice': [2205], 'L.M.': [2206], 'Simonson': [2207], 'T.': [2208, 2554, 3214, 3222], 'Warren': [2209], 'G.L.': [2210], '1998;': [2217], '54:': [2218], '905-921Crossref': [2219], '(16979)': [2222], 'Further': [2225], 'refinement': [2226, 2233], 'REFMAC': [2230], 'TLS': [2232], 'riding': [2235], 'hydrogens': [2236], '(26Murshudov': [2237], 'G.N.': [2238], 'Vagin': [2239], 'A.A.': [2240], 'Dodson': [2241], 'E.J.': [2242], '53:': [2250], '240-255Crossref': [2251], '(13911)': [2254], 'consists': [2260], 'residues': [2262, 2284, 3889, 3906, 4033, 4292, 4394], 'Rfree': [2266], '25.7%': [2269], 'Rwork': [2271], '22.1%.': [2274], 'space': [2276], 'P3221,': [2279], '87.6%': [2281], 'most': [2292, 4591], 'favored': [2293], 'area': [2294, 3260], 'Ramachandran': [2297], 'plot': [2298], '(additional': [2299], 'statistics': [2301], 'supplemental': [2305, 3366], 'Table': [2306], 'S1).': [2307, 3082, 3848], 'atomic': [2309], 'coordinates': [2310], 'deposited': [2312], 'Data': [2316], 'Bank': [2317], '(code': [2318], '3dba).': [2319], 'Preparation': [2320], 'Isotopically': [2322], 'Labeled': [2323], 'Experiments—Uniformly': [2329], '15N-labeled': [2330, 3624], '15N-NH4Cl': [2344], '(Cambridge': [2345], 'Isotope': [2346], 'Laboratories).': [2347], 'Cell': [2348], 'nickel': [2351, 2362], 'chromatography': [2354, 3836], 'carried': [2356], 'out': [2357], 'described': [2359, 3526], 'above.': [2360], 'eluate': [2364], 'injected': [2368], 'onto': [2369, 3894], 'Superdex': [2371], '75': [2372], 'column.': [2373], '150': [2380], 'phosphate,': [2386, 2693], '7.0,': [2388, 2695], 'EDTA.': [2391], 'fractionation,': [2393], 'dithiothreitol': [2394, 2698], 'added.': [2403, 2415], 'samples': [2405], '∼150': [2409], 'μm,': [2410], '10%': [2412], 'D2O': [2413], 'added': [2425], 'spectrum': [2428, 3675], 'form.': [2432], '1H,15N': [2433, 2533, 3620], 'HSQC': [2434, 3621], 'spectra': [2435, 2452, 3622, 3701, 3735], 'Varian': [2443], '800-MHz': [2444], 'INOVA': [2445], 'spectrometer': [2446, 2674], 'equipped': [2447], '1H-13C,15N-cold': [2449], 'probe.': [2450], 'All': [2451, 4513], 'processed': [2454], 'analyzed': [2456], 'NMRDraw': [2458], '(27Delaglio': [2459], 'F.': [2460], 'Grzesiek': [2461], 'Vuister': [2463], 'G.W.': [2464], 'Zhu': [2465], 'G.': [2466, 2550], 'Pfeifer': [2467], 'Bax': [2469], 'Biomol.': [2472, 2489, 2632], 'NMR.': [2473, 2490, 2633, 3021], '1995;': [2474, 2655], '6:': [2475], '277-293Crossref': [2476], '(11632)': [2479], 'NMRView': [2483, 2626], '(28Johnson': [2484, 2627], 'B.A.': [2485, 2628], 'Blevins': [2486, 2629], 'R.A.': [2487, 2630], '4:': [2492, 2635], '603-614Crossref': [2493, 2636], '(2686)': [2496, 2639], 'Determination': [2499], 'Rotational': [2502], 'Correlation': [2503], 'Time—To': [2504], 'determine': [2505], 'rotational': [2507, 3007], 'time': [2509, 2751, 3009], '0.7': [2511], 'presence': [2518, 2703, 3632], 'measured': [2522, 2735, 3756], '15N': [2523, 3017], 'spin': [2524], 'relaxation': [2525, 2579, 2597, 3018], 'parameters': [2526], '(R1,': [2527], 'R2)': [2528], 'steady-state': [2531], 'NOEs': [2534], 'standard': [2536], 'pulse': [2537], 'sequences': [2538, 3857, 3868, 4447, 4593], '(29Farrow': [2539], 'Muhandiram': [2541], 'Singer': [2543], 'A.U.': [2544], 'Pascal': [2545], 'S.M.': [2546], 'Kay': [2547, 2557], 'C.M.': [2548, 4255], 'Gish': [2549], 'Shoelson': [2551], 'Pawson': [2553], 'Forman-Kay': [2555], 'L.E.': [2558], 'Biochemistry.': [2559, 3997], '33:': [2561], '5984-6003Crossref': [2562], '(2018)': [2565], 'Bruker': [2573], '500': [2574], 'MHz': [2575], 'DMX': [2576], 'spectrometer.': [2577], '15N-T1': [2578], 'delays': [2580, 2593, 2598, 2610], '10,': [2582], '50,': [2583], '100,': [2584], '200,': [2585], '400,': [2586], '600,': [2587], '800,': [2588], '1000': [2590], 'ms': [2591, 2608], '(underlined': [2592, 2609], 'duplicated).': [2595, 2612], '15N-T2': [2596], '17.2,': [2600], '34.4,': [2601], '51.7,': [2602], '69.0,': [2603], '86.2,': [2604], '103.5,': [2605], '120.7': [2607], 'Only': [2613], 'resolved': [2615], 'resonances': [2616, 3662, 3672], 'dynamics': [2621], 'analysis': [2622], '(85': [2623], 'resonances)': [2624], 'Modelfree': [2643], '4.15': [2644], '(30Mandel': [2645], 'A.M.': [2646], 'Akke': [2647], 'Palmer': [2649], 'III,': [2650], 'A.G.': [2651], '246:': [2656], '144-163Crossref': [2657], '(906)': [2660], 'Circular': [2663, 3699], 'Dichroism': [2664], 'Studies—Circular': [2665], '62A': [2672], 'DS': [2673], '(Aviv': [2675], 'Biomedical).': [2676], 'Spectra': [2677], '10–20': [2681], 'absence': [2701, 3583, 3630], '(cuvette': [2708], 'path': [2709], 'length,': [2710], 'cm).': [2712], 'monitor': [2714], 'temperature-dependent': [2716], 'denaturation': [2717], 'thermal': [2719], 'scans,': [2720], 'ellipticity': [2721, 3758], 'α-helical': [2724, 3719, 3761], '222': [2727, 3764], 'nm': [2728, 3765], 'range': [2738, 3036], '10–85': [2740], 'steps': [2743], 'every': [2744], '60-s': [2749], 'equilibration': [2750], 'step.': [2754], 'Overall': [2755, 4095], 'Domain': [2757, 4097], 'Fold—The': [2758, 4098], 'domain,': [2767], 'resolution': [2771], 'Å,': [2774], 'displays': [2775], 'typical': [2777, 3037], 'six-stranded': [2783], 'antiparallel': [2784], 'β-sheet': [2785, 2795, 2874], 'arranged': [2786], 'strand': [2789], 'order': [2790], '3-2-1-6-5-4': [2791], '(Fig.': [2792, 2976, 3119, 3363, 3635, 3771, 3890, 3919, 3950, 4076, 4416, 4476, 4594], '1A).': [2793], 'provides': [2796, 3370, 3489, 3507, 4411, 4548, 4567], 'floor,': [2798], 'helices': [2802], 'α3': [2803, 3322], 'α4': [2805], 'comprise': [2806], 'roof': [2808], 'deeply': [2811], 'buried': [2812, 3265], 'pocket.': [2814, 2882, 3298], 'helical': [2816, 4176, 4246], 'dipole': [2817], 'α3,': [2819, 3872], 'β3': [2823, 2886], 'β4': [2825, 2844], 'primary': [2828], 'structure,': [2829, 3721], 'points': [2830, 3323], 'toward': [2831, 3324, 3944], 'phosphate': [2833, 3307, 3326, 3332], 'bound': [2837, 3115], 'molecule.': [2839, 2853], 'α4,': [2840], 'β5': [2846], 'sequence,': [2848], 'sits': [2849], 'atop': [2850], 'Helices': [2854], 'α1': [2855, 2966], 'α2': [2857], 'precede': [2858], 'β-strand': [2861], 'and,': [2862], 'together': [2863], 'α5,': [2865], 'three-helix': [2868], 'bundle': [2869], 'packs': [2871], 'against': [2872, 4425, 4688], 'opposite': [2877, 4064], 'side': [2878, 3382, 3476, 3486, 3554, 4065, 4195, 4216, 4301, 4345, 4481, 4504, 4633], 'Strands': [2883], 'β2': [2884], 'connected': [2888], '18-residue': [2891], 'loop': [2892], 'includes': [2894], 'short': [2896, 4175], 'α-helix': [2897], '(α2/3).': [2898], 'Excluding': [2899], 'helix': [2900, 2965, 3321, 3342], 'α1,': [2901], 'both': [2902, 3645, 3703, 3713, 3802, 4429], 'unit': [2907, 2943], 'superimpose': [2908], 'root': [2912], 'mean': [2913], 'square': [2914], 'deviation': [2915], '149': [2920], 'equivalent': [2921, 4405, 4540, 4572, 4611], 'C-α': [2922], 'atoms.': [2923], 'homodimer.': [2940], 'do': [2951, 3741], 'dimerize': [2953], 'lattice': [2962], 'symmetry.': [2963], 'Notably,': [2964], 'different': [2970, 3653, 4454, 4654], '1A)': [2977], 'because': [2978], 'packing': [2982], 'environment': [2983], 'monomer': [2986, 3093], 'lack': [2988], 'restrain': [2994], 'helix.': [2996], 'confirm': [2998], 'solution,': [3003], 'τc': [3010, 3026], '15N-PDE6C': [3013], 'measurements': [3019], 'calculated': [3023], 'value': [3024], '12.4': [3028], 'ns': [3029], 'proteins': [3039], '(∼20': [3043], 'kDa),': [3044], 'therefore': [3045, 4419], 'confirming': [3046], 'solution': [3053, 4229], 'millimolar': [3055, 3587], 'concentrations.': [3056], 'Apo': [3057], 'elute': [3063], 'same': [3066], 'volume': [3068], 'shape': [3074, 3845], 'analytical': [3076, 3833], 'exclusion': [3078, 3835], 'chromatograms': [3079], '(supplemental': [3080, 3314, 3846], 'Fig.': [3081, 3315, 3367, 3847, 4022], 'Together,': [3083], 'indicate': [3086], 'intrinsically': [3091], 'alter': [3100], 'oligomeric': [3102], 'Site': [3108], 'A—Cyclic': [3112], 'GMP': [3113], 'anti-conformation': [3118], '1B),': [3120], 'cAMP': [3158, 4317, 4426, 4659, 4689], 'cyanobacterial': [3166], 'cyclase': [3168], 'cyaB2': [3169], '(31Martinez': [3170, 4142], 'Bruder': [3172, 4144], 'Schultz': [3174, 3178, 4146, 4150], 'Zheng': [3176, 4148], 'Linder': [3182, 4154], 'J.U.': [3183, 4155], '102:': [3192, 4164], '3082-3087Crossref': [3193, 4165], '(75)': [3196, 4168], 'PDE10A': [3200], '(32Handa': [3203], 'Mizohata': [3205], 'Kishishita': [3207], 'Toyama': [3209], 'Morita': [3211], 'Uchikubo-Kamo': [3213], 'Akasaka': [3215], 'Omori': [3217], 'Terada': [3221], 'Shirouzu': [3223], 'Yokoyama': [3225], '283:': [3231, 4268], '19657-19664Abstract': [3232], '(55)': [3240], 'Similar': [3243], 'previously': [3246, 3962, 4114, 4140], 'solved': [3247], 'nucleotide-binding': [3249, 4117], 'nearly': [3252], 'entire': [3254], '493': [3255], 'Å2': [3256], 'solvent-accessible': [3258, 3910], 'PDE6C,': [3267, 4179, 4403], 'closed': [3276], 'forms': [3279], 'Because': [3283], 'lower': [3286], 'factor,': [3289], 'use': [3291], 'chain': [3292, 3383, 3477, 3487, 4346, 4505, 4634], 'describe': [3295], 'electron': [3300], 'shows': [3303], '3′,5′-cyclic': [3306], 'chair': [3312], 'conformation': [3313], 'S2).': [3316], 'N-terminal': [3318], 'end': [3319], 'group,': [3327], 'bringing': [3328], 'negatively': [3330, 3946, 4029], 'charged': [3331, 3926, 3947, 4030, 4073], 'adjacent': [3334], 'partial': [3337, 3427], 'positive': [3338], 'charge': [3339, 3429], 'dipole.': [3343], 'contacts': [3349, 4380, 4506, 4635], 'defined': [3356], 'series': [3359], 'protein-ligand': [3361, 3374, 3527, 4413], 'interactions': [3362, 3532, 4569], '1B': [3364], 'S3).': [3368], 'Asn-116': [3369, 3415, 3441, 4209, 4401, 4458], 'important': [3372, 3535], 'cGMP-specific': [3373], 'bonds.': [3376, 4227], 'carbonyl': [3378, 3410, 3432, 4207, 4367], 'oxygen': [3379, 3411, 3433, 4484], '2.7-Å': [3386], 'bond': [3388, 3406, 3452, 3462, 3513, 3529, 4362, 4491, 4603, 4622, 4630], 'protonated': [3391], 'N-1': [3392, 4508], 'ring,': [3396, 4377, 4563], 'backbone': [3399, 4206, 4357], 'amide': [3400, 3661, 4358], '2.9': [3403], 'O-6': [3409, 4366], 'locked': [3417], 'position': [3419, 3843, 4221], '3.0-Å': [3422], 'bridge': [3424], 'negative': [3428, 4423], 'guanidine': [3436], 'Arg-95.': [3439], 'Finally,': [3440], 'provide': [3443, 4223], 'yet': [3444], 'another': [3445, 3945], 'determinant': [3447, 4424], 'water-mediated': [3450, 3491, 4386, 4628], 'N-2': [3455, 3465, 3498, 4383], 'amino': [3456, 3466, 3499, 4074, 4573], '(via': [3458, 3494], 'HOH-264).': [3459], 'Another': [3460], 'Thr-172,': [3479], '3.4': [3482], 'away.': [3484], 'HOH-254)': [3495], 'N-3': [3503], 'nitrogen.': [3505], 'Ser-97': [3506], 'additional': [3509], '2.7': [3510], 'N-7': [3515], 'addition': [3523, 3783], 'network,': [3530], 'hydrophobic': [3531, 4032, 4568], 'play': [3533], 'role': [3536], 'definition': [3539], 'pocket': [3543], 'orientation.': [3546], 'sandwiched': [3551], 'chains': [3555, 4196, 4219, 4302, 4482], 'Phe-99,': [3557], 'Leu-115,': [3558, 4398], 'Leu-168,': [3559], 'Tyr-174,': [3560], 'Leu-197.': [3562], 'Conformational': [3563], 'Change': [3564], 'cGMP—We': [3568], 'purify': [3572], 'concentrate': [3574], 'concentrations': [3588], 'unsuccessful': [3592], 'producing': [3594], 'diffraction-quality': [3595], 'crystals.': [3596], 'Therefore,': [3597], 'two-dimensional': [3600], 'spectroscopy': [3602], 'investigate': [3604], 'forms.': [3616], 'An': [3617, 4024], 'overlay': [3618], '2A)': [3636], 'folded': [3643], 'cases.': [3646], 'However,': [3647], 'states': [3650, 3704, 3740, 3803], 'adopt': [3651], 'conformations,': [3654], 'overwhelming': [3657], 'majority': [3658], 'perturbed': [3664], 'line': [3669], 'width.': [3670], 'vary': [3680, 4684], 'widely': [3681], 'intensities,': [3684], 'indicative': [3685], 'exchange': [3687], 'multiple': [3689], 'states,': [3690], 'subset': [3693], 'peaks': [3695], 'broadened': [3696], 'beyond': [3697], 'detection.': [3698], 'virtually': [3710], 'indistinguishable': [3711], 'strong': [3716], 'indicated': [3722], 'minima': [3724], '208': [3726], '218': [3728], 'nm.': [3729], 'negligible': [3731], 'difference': [3732, 3840, 4122], 'suggests': [3736], 'element': [3749], 'content.': [3750], 'assess': [3752], 'stability,': [3754], '2B).': [3772], 'observed': [3774], 'melting': [3780], 'considerable': [3787], 'thermodynamic': [3788], 'stabilization': [3789], 'supports': [3798], 'hypothesis': [3800], 'global': [3807], 'tertiary': [3808], 'rather': [3810], 'local': [3813], 'unfolding': [3814], 'elements.': [3818], 'lead': [3825], 'hydrodynamic': [3830], 'behavior': [3831], 'observable': [3839], 'Conserved': [3849], 'Interaction': [3850], 'Surface—An': [3851], 'alignment': [3852, 4442], 'stretches': [3865], 'β1': [3870], 'encompass': [3874], 'β2,': [3875], 'α2/3,': [3876, 4181], 'β3,': [3878], 'strongly': [3880], 'number': [3885], '3A).': [3891, 4477, 4595], 'When': [3892], 'plotted': [3893], 'these': [3904, 4393], 'contiguous': [3909], '3B).': [3920], 'residues.': [3927], 'Arg-102': [3928], 'Arg-104': [3930], 'surrounded': [3932], 'Glu-109,': [3934], 'Asp-131,': [3935], 'Glu-133.': [3937], 'Val-135': [3938], 'Pro-137': [3940], 'extend': [3941], 'residue,': [3948], 'Asp-139': [3949], '3C,': [3951, 4077], 'left': [3952], 'panel).': [3953], 'Ile-140,': [3954], 'Gly-141,': [3955], 'His-163,': [3957], 'all': [3959, 4479], 'proposed': [3963], 'Pγ-binding': [3971], '(33Muradov': [3973], 'Boyd': [3975], 'K.K.': [3976], '44:': [3982], '2437-2444Crossref': [3983], '(24)': [3986], '34Muradov': [3989], 'K.G.': [3990], 'Granovsky': [3991], 'Schey': [3993], 'K.L.': [3994], '41:': [3999], '3884-3890Crossref': [4000], '(40)': [4003], 'close': [4014], 'proximity': [4015], 'it': [4017, 4082, 4493, 4555, 4586], '(highlighted': [4018], 'magenta': [4020], '3C).': [4023], 'elongated': [4025], 'numerous': [4028], 'can': [4034, 4467], 'drawn': [4036], 'Asp-131': [4038], 'His-163': [4040], 'responsible': [4044], 'interaction': [4047, 4089], 'smaller': [4056], 'It': [4069], 'positively': [4072], 'acids': [4075], 'right': [4078], 'panel)': [4079], 'likely': [4085, 4495, 4547], 'Comparison': [4093, 4280], 'very': [4108], 'topology': [4112], 'characterized': [4115, 4515], 'largest': [4121], 'published': [4125], 'structures': [4128], 'length': [4131], 'sequence': [4133, 4441], 'β2-β3': [4136], 'loop,': [4137], 'discussed': [4141], 'stretch': [4172], 'termed': [4180], 'positioned': [4184], 'stabilize': [4186], 'cGMP-contacting': [4190], 'residue.': [4191], 'particular,': [4193], 'Ser-121': [4198], 'Asn-126': [4200], 'make': [4201, 4502], 'lock': [4214], 'main': [4218], 'nucleotide-selective': [4225], 'cGMP-selective': [4238], '(35Heikaus': [4248], 'C.C.': [4249], 'Stout': [4250], 'Sekharan': [4252], 'M.R.': [4253], 'Eakin': [4254], 'Rajagopal': [4256], 'Brzovic': [4258], 'P.S.': [4259], 'Klevit': [4262], 'R.E.': [4263], '22749-22759Abstract': [4269], '(34)': [4277], 'Pockets': [4283], 'PDE2A—Systematic': [4287], 'alanine': [4288], 'mutations': [4289], 'three': [4299, 4480], 'guanine-binding': [4300], '(Asp-439,': [4303], 'Phe-438,': [4304], 'Thr-488)': [4306], 'required': [4308], '∼30-fold': [4311], 'higher': [4312], '(36Wu': [4318, 4693], 'Martinez': [4322, 4697], 'Ikeda': [4324, 4699], '279:': [4332], '37928-37938Abstract': [4333], '(69)': [4341], 'Asp-439': [4348, 4408], 'hydrogen-bound': [4350], 'N-1,': [4354], 'donor': [4363], 'guanine.': [4370], 'Phe-438': [4371, 4542, 4546], 'base-stacked': [4373], 'Thr-488': [4379], 'bond.': [4388], 'correspond': [4395], 'Thr-172.': [4400], 'residue': [4406, 4612], 'PDE2A,': [4410, 4614], '1B)': [4417], 'serves': [4420], 'cannot': [4432], 'satisfied': [4434], 'adenine': [4437], 'ring.': [4438, 4512], 'Surprisingly,': [4439], 'PDE6A,': [4449], '-B,': [4450], '-C': [4452], 'species': [4455], 'variable': [4460], 'gene': [4464], 'family': [4465], 'Asn,': [4470, 4498], 'Asp,': [4472], 'Ser': [4475], 'capable': [4486], 'serving': [4488], 'acceptors,': [4492], 'Ser,': [4497], 'Asp': [4500, 4531], '(PDE2A': [4519, 4692], 'B,': [4521], 'PDE11A': [4526], 'analogous': [4534], 'position.': [4535], 'Leu-115': [4536, 4564], 'PDE2A.': [4544, 4645], 'Whereas': [4545], 'aromatic': [4549], 'π': [4550], '-π': [4551], '-base': [4552], 'stacking': [4553], 'aligned': [4557], 'instead.': [4570, 4631], '(isoforms': [4578], 'Phe,': [4584], 'Leu': [4589], 'Thr-172': [4596], 'direct': [4601, 4620], 'N-2,': [4607], 'Thr-488,': [4609], 'too': [4616], 'far': [4617], '(3.8': [4623], 'Other': [4632], 'Determinants': [4647], 'Affinity': [4649], 'Specificity—GAF': [4651], 'PDEs': [4655], 'wide': [4662], 'affinities': [4665, 4679], 'specificities.': [4667], 'nanomolar': [4678], 'selectivity': [4687], '30-fold': [4691]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2067191902', 'counts_by_year': [{'year': 2022, 'cited_by_count': 2}, {'year': 2021, 'cited_by_count': 3}, {'year': 2020, 'cited_by_count': 1}, {'year': 2019, 'cited_by_count': 4}, {'year': 2017, 'cited_by_count': 4}, {'year': 2015, 'cited_by_count': 1}, {'year': 2014, 'cited_by_count': 5}, {'year': 2013, 'cited_by_count': 2}, {'year': 2012, 'cited_by_count': 5}], 'updated_date': '2024-12-11T08:09:58.385187', 'created_date': '2016-06-24'}