Document 0166
 DOCN  M95A0166
 TI    Flexibility and function in HIV-1 protease [see comments]
 DT    9510
 AU    Nicholson LK; Yamazaki T; Torchia DA; Grzesiek S; Bax A; Stahl SJ;
       Kaufman JD; Wingfield PT; Lam PY; Jadhav PK; et al; Molecular Structural
       Biology Unit, National Institute of Dental; Research, National
       Institutes of Health, Bethesda, Maryland; 20892, USA.
 SO    Nat Struct Biol. 1995 Apr;2(4):274-80. Unique Identifier : AIDSLINE
       MED/95316676
 CM    Comment in: Nat Struct Biol 1995 Apr;2(4):255-7
 AB    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 15N spin
       relaxation 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 amplitude motions on the ps to ns
       time scale, while the tips of the flaps undergo a conformational
       exchange on the microsecond 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.
 DE    Amino Acid Sequence  Binding Sites  Comparative Study  HIV
       Protease/*CHEMISTRY/*METABOLISM  HIV Protease
       Inhibitors/*CHEMISTRY/METABOLISM  Isoleucine/*ANALOGS &
       DERIVATIVES/CHEMISTRY/METABOLISM  Kinetics  Models, Molecular  Nitrogen
       Isotopes  Nuclear Magnetic Resonance/METHODS  *Protein Conformation
       Recombinant Proteins/CHEMISTRY/METABOLISM  Support, U.S. Gov't, P.H.S.
       Urea/*ANALOGS & DERIVATIVES/CHEMISTRY  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).