Document 0164
 DOCN  M95A0164
 TI    Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside
       inhibitors.
 DT    9510
 AU    Esnouf R; Ren J; Ross C; Jones Y; Stammers D; Stuart D; Laboratory of
       Molecular Biophysics, Oxford, UK.
 SO    Nat Struct Biol. 1995 Apr;2(4):303-8. Unique Identifier : AIDSLINE
       MED/95316680
 AB    The structure of unliganded HIV-1 reverse transcriptase has been
       determined at 2.35 A resolution and refined to an R-factor of 0.219 (for
       all data) with good stereochemistry. The unliganded structure was
       produced by soaking out a weak binding non-nucleoside inhibitor, HEPT,
       from pregrown crystals. Comparison with the structures of four different
       RT and non-nucleoside inhibitor complexes reveals that only minor domain
       rearrangements occur, but there is a significant repositioning of a
       three-stranded beta-sheet in the p66 subunit (containing the catalytic
       aspartic acid residues 110, 185 and 186) with respect to the rest of the
       polymerase site. This suggests that NNIs inhibit RT by locking the
       polymerase active site in an inactive conformation, reminiscent of the
       conformation observed in the inactive p51 subunit.
 DE    Antiviral Agents/CHEMISTRY/*PHARMACOLOGY  Binding Sites
       Crystallography, X-Ray  HIV-1/DRUG EFFECTS/ENZYMOLOGY  Models, Molecular
       *Protein Conformation  *Protein Structure, Secondary  Reverse
       Transcriptase/*ANTAGONISTS & INHIB/*CHEMISTRY  Support, Non-U.S. Gov't
       Thymine/*ANALOGS & DERIVATIVES/CHEMISTRY/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).