Document 0070
 DOCN  M9470070
 TI    Alternative native flap conformation revealed by 2.3 A resolution
       structure of SIV proteinase.
 DT    9409
 AU    Wilderspin AF; Sugrue RJ; Department of Crystallography, Birkbeck
       College, London, England.
 SO    J Mol Biol. 1994 May 27;239(1):97-103. Unique Identifier : AIDSLINE
       MED/94254094
 AB    A large conformational change is observed between HIV-1 proteinase in
       the ligand-free state and in complexes with transition-state inhibitors.
       Crystal structures of this enzyme have either the flaps open for the
       native or ligand-free enzyme or the flaps closed for peptidomimetic
       ligand-bound enzyme. We describe the structure of native recombinant SIV
       proteinase which like other retroviral proteinases crystallizes as a
       perfect 2-fold symmetric dimer but in a different crystal packing
       arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the
       ligand-free state adopts the closed flaps conformation, demonstrating
       that ligand binding is not a prerequisite for the closed flaps
       conformation. The catalytic water was clearly observed between the two
       aspartates which were not perfectly co-planar, and in this structure the
       active site cleft is more restricted than for either inhibitor bound or
       ligand-free HIV-1 proteinase. Accommodation of two bulkier side-chains
       in the simian enzyme core has resulted in a more exposed N terminus than
       for HIV-1 PR which we predict could enhance autocatalytic cleavage at
       the N terminus.
 DE    Amino Acid Sequence  Aspartic Proteinases/*CHEMISTRY/GENETICS  Binding
       Sites  HIV Protease/GENETICS  Models, Molecular  Molecular Sequence Data
       Molecular Structure  *Protein Conformation  Sequence Alignment  Support,
       Non-U.S. Gov't  SIV/*ENZYMOLOGY  JOURNAL ARTICLE

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