Document 0317
 DOCN  M9610317
 TI    High-resolution structure of the catalytic domain of avian sarcoma virus
       integrase.
 DT    9601
 AU    Bujacz G; Jaskolski M; Alexandratos J; Wlodawer A; Merkel G; Katz RA;
       Skalka AM; Macromolecular Structure Laboratory, NCI-Frederick Cancer;
       Research and Development Center, MD 21702, USA.
 SO    J Mol Biol. 1995 Oct 20;253(2):333-46. Unique Identifier : AIDSLINE
       MED/96036765
 AB    Retroviral integrase (IN) functions to insert retroviral DNA into the
       host cell chromosome in a highly coordinated manner. IN catalyzes two
       biochemically separable reactions: processing of the viral DNA ends and
       joining of these ends to the host DNA. Previous studies suggested that
       these two reactions are chemically similar and are carried out by a
       single active site that is characterized by a highly conserved
       constellation of carboxylate residues, the D,D(35)E motif. We report
       here the crystal structure of the isolated catalytic domain of avian
       sarcoma virus (ASV) IN, solved using multiwavelength anomalous
       diffraction data for a selenomethionine derivative and refined at 1.7 A
       resolution. The protein is a crystallographic dimer with each monomer
       featuring a five-stranded mixed beta-sheet region surrounded by five
       alpha-helices. Based on the general fold and the arrangement of
       catalytic carboxylate residues, it is apparent that ASV IN is a member
       of a superfamily of proteins that also includes two types of nucleases,
       RuvC and RNase H. The general fold and the dimer interface are similar
       to those of the analogous domain of HIV-1 IN, whose crystal structure
       has been determined at 2.5 A resolution. However, the ASV IN structure
       is more complete in that all three critical carboxylic acids, Asp64,
       Asp121 and Glu157, are ordered. The ordered active site and the
       considerably higher resolution of the present structure are all
       important to an understanding of the mechanism of retroviral DNA
       integration, as well as for designing antiviral agents that may be
       effective against HIV.
 DE    Amino Acid Sequence  Aspartic Acid  Bacterial Proteins/CHEMISTRY
       Binding Sites  Comparative Study  Crystallization  Crystallography,
       X-Ray  DNA Nucleotidyltransferases/*CHEMISTRY/ISOLATION & PURIF/
       METABOLISM  Endodeoxyribonucleases/CHEMISTRY  Glutamic Acid
       HIV/ENZYMOLOGY  Macromolecular Systems  Models, Molecular  Molecular
       Sequence Data  *Protein Folding  *Protein Structure, Secondary
       Ribonuclease H, Calf Thymus/CHEMISTRY  Sarcoma Viruses,
       Avian/*ENZYMOLOGY  Sequence Homology, Amino Acid  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Virus Integration  JOURNAL ARTICLE

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