Document 0633
 DOCN  M9550633
 TI    An essential interaction between distinct domains of HIV-1 integrase
       mediates assembly of the active multimer.
 DT    9505
 AU    Ellison V; Gerton J; Vincent KA; Brown PO; Department of Biochemistry,
       Stanford University, California; 94305.
 SO    J Biol Chem. 1995 Feb 17;270(7):3320-6. Unique Identifier : AIDSLINE
       MED/95155427
 AB    Integrase mediates integration of the retroviral genome into a host cell
       chromosome, an essential step in the viral life cycle. In vitro, a
       stable complex containing only purified human immunodeficiency virus
       (HIV) integrase and a model viral DNA substrate processively executes
       the 3'-end processing and DNA joining steps in the integration reaction.
       We examined the relationship of three essential components of the HIV
       integrase: the HHCC domain, a putative zinc-finger near the N terminus;
       the phylogenetically conserved DD35E motif, which defines the catalytic
       domain; and a feature recognized by its sensitivity to the alkylating
       agent N-ethylmaleimide (NEM). HIV integrase is a multimer, and these
       three components can be distributed among at least two subunits of the
       multimeric enzyme. The components function asymmetrically in the active
       multimer; the DD35E motif and NEM-sensitive site are required in trans
       to the HHCC region. A divalent cation-dependent interaction involving
       the NEM-sensitive site of one integrase subunit and the HHCC region of
       another subunit points to a role for these two features of integrase in
       multimer assembly. Deletion of the HHCC domain, or modification of
       integrase with NEM, impaired the assembly of a stable complex between
       integrase and viral DNA, suggesting that this initial step in the
       integration pathway requires assembly of the active integrase multimer.
 DE    Amino Acid Sequence  Base Sequence  Chlorides/PHARMACOLOGY  Comparative
       Study  Dithiothreitol/PHARMACOLOGY  DNA
       Nucleotidyltransferases/BIOSYNTHESIS/*CHEMISTRY/*METABOLISM
       Ethylmaleimide/PHARMACOLOGY  Genetic Complementation Test
       HIV-1/*ENZYMOLOGY/GENETICS  Kinetics  Macromolecular Systems  Magnesium
       Chloride/PHARMACOLOGY  Manganese Compounds/PHARMACOLOGY  Models,
       Structural  Molecular Sequence Data  Mutagenesis  Mutagenesis,
       Site-Directed  Oligodeoxyribonucleotides/METABOLISM  Point Mutation
       Sequence Deletion  Substrate Specificity  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).