A COMPARISON OF THE CONFORMATIONS OF THE 5'-TRIPHOSPHATES OF ZIDOVUDINE (AZT) AND THYMIDINE BOUND TO HIV-1 REVERSE-TRANSCRIPTASE

被引:32
作者
PAINTER, GR [1 ]
AULABAUGH, AE [1 ]
ANDREWS, CW [1 ]
机构
[1] BURROUGHS WELLCOME CO,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
关键词
D O I
10.1006/bbrc.1993.1339
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear Overhauser effect experiments were performed at 500 MHz to determine the conformations of AZTTP and dTTP when bound to HIV-1 reverse transcriptase. The conformations of both ligands were found to be similar in the bound state. The orientation of the glycosidic angle is anti (x = -120° ± 12 for AZTTP and -110° ± 12 for dTTP), γ is + sc and the pucker of the 3'-azido-2', 3'-dideoxy- and 2'-deoxyribose rings is predominantly C4' exo (P = 60° ± 10 for AZTTP and 55° ± 8 for dTTP). These results indicate that the unusual C4'endo/C3'exo pucker (P = 215°) reported for the dideoxyribose ring of AZT in the solid state does not play a role in the interaction of HIV-1 reverse transcriptase with AZTTP. © 1993 Academic Press, Inc.
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页码:1166 / 1171
页数:6
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