FLEXIBILITY AND FUNCTION IN HIV-1 PROTEASE

被引:235
作者
NICHOLSON, LK
YAMAZAKI, T
TORCHIA, DA
GRZESIEK, S
BAX, A
STAHL, SJ
KAUFMAN, JD
WINGFIELD, PT
LAM, PYS
JADHAV, PK
HODGE, CN
DOMAILLE, PJ
CHANG, CH
机构
[1] NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892
[2] NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892
[3] DUPONT MERCK PHARMACEUT CO,DEPT CHEM & PHYS SCI,WILMINGTON,DE 19880
来源
NATURE STRUCTURAL BIOLOGY | 1995年 / 2卷 / 04期
关键词
D O I
10.1038/nsb0495-274
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
HIV protease is a homodimeric protein whose activity is essential to viral function. We have investigated the molecular dynamics of the HIV protease, thought to be important for proteinase function, bound to high affinity inhibitors using NMR techniques. Analysis of N-15 spin refaxation parameters, of all but 13 backbone amide sites, reveals the presence of significant internal motions of the protein backbone. In particular, the flaps that cover the proteins active site of the protein have terminal loops that undergo large aCnpIitude motions on the ps to ns time scale, while the tips of the flaps undergo a conformational exchange on the mu s time scale. This enforces the idea that the flaps of the proteinase are flexible structures that facilitate function by permitting substrate access to and product release from the active site of the enzyme.
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页码:274 / 280
页数:7
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