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.
引用
收藏
页码:274 / 280
页数:7
相关论文
共 42 条
  • [1] ABRAGAM A, 1961, PRINCIPLES NUCLEAR M
  • [2] PRIMARY STRUCTURE EFFECTS ON PEPTIDE GROUP HYDROGEN-EXCHANGE
    BAI, YW
    MILNE, JS
    MAYNE, L
    ENGLANDER, SW
    [J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1993, 17 (01): : 75 - 86
  • [3] BACKBONE DYNAMICS OF CALMODULIN STUDIED BY N-15 RELAXATION USING INVERSE DETECTED 2-DIMENSIONAL NMR-SPECTROSCOPY - THE CENTRAL HELIX IS FLEXIBLE
    BARBATO, G
    IKURA, M
    KAY, LE
    PASTOR, RW
    BAX, A
    [J]. BIOCHEMISTRY, 1992, 31 (23) : 5269 - 5278
  • [4] INFLUENCE OF CROSS-CORRELATION BETWEEN DIPOLAR AND ANISOTROPIC CHEMICAL-SHIFT RELAXATION MECHANISMS UPON LONGITUDINAL RELAXATION RATES OF N-15 IN MACROMOLECULES
    BOYD, J
    HOMMEL, U
    CAMPBELL, ID
    [J]. CHEMICAL PHYSICS LETTERS, 1990, 175 (05) : 477 - 482
  • [5] HIGH-LEVEL SYNTHESIS OF RECOMBINANT HIV-1 PROTEASE AND THE RECOVERY OF ACTIVE ENZYME FROM INCLUSION-BODIES
    CHENG, YSE
    MCGOWAN, MH
    KETTNER, CA
    SCHLOSS, JV
    ERICKSONVIITANEN, S
    YIN, FH
    [J]. GENE, 1990, 87 (02) : 243 - 248
  • [6] ANALYSIS OF THE BACKBONE DYNAMICS OF INTERLEUKIN-1-BETA USING 2-DIMENSIONAL INVERSE DETECTED HETERONUCLEAR N-15-H-1 NMR-SPECTROSCOPY
    CLORE, GM
    DRISCOLL, PC
    WINGFIELD, PT
    GRONENBORN, AM
    [J]. BIOCHEMISTRY, 1990, 29 (32) : 7387 - 7401
  • [7] DEVIATIONS FROM THE SIMPLE 2-PARAMETER MODEL-FREE APPROACH TO THE INTERPRETATION OF N-15 NUCLEAR MAGNETIC-RELAXATION OF PROTEINS
    CLORE, GM
    SZABO, A
    BAX, A
    KAY, LE
    DRISCOLL, PC
    GRONENBORN, AM
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (12) : 4989 - 4991
  • [8] RELAXATION STUDY OF THE BACKBONE DYNAMICS OF HUMAN PROFILIN BY 2-DIMENSIONAL H-1-N-15 NMR
    CONSTANTINE, KL
    FRIEDRICHS, MS
    BELL, AJ
    LAVOIE, TB
    MUELLER, L
    METZLER, WJ
    [J]. FEBS LETTERS, 1993, 336 (03) : 457 - 461
  • [9] MODEL-INDEPENDENT AND MODEL-DEPENDENT ANALYSIS OF THE GLOBAL AND INTERNAL DYNAMICS OF CYCLOSPORINE-A
    DELLWO, MJ
    WAND, AJ
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (13) : 4571 - 4578
  • [10] Farrar T. C., 1971, PULSE FOURIER TRANSF, P1