Document 0637
 DOCN  M9650637
 TI    The metal ion-induced cooperative binding of HIV-1 integrase to DNA
       exhibits a marked preference for Mn(II) rather than Mg(II).
 DT    9605
 AU    Pemberton IK; Buckle M; Buc H; Unite de Physicochimie des Macromolecules
       Biologiques CNRS URA; 1149, Institut Pasteur, Paris, France.
 SO    J Biol Chem. 1996 Jan 19;271(3):1498-506. Unique Identifier : AIDSLINE
       MED/96139481
 AB    In this investigation, we examine the interaction between the human
       immunodeficiency virus type I integrase and oligonucleotides that
       reflect the sequences of the extreme termini of the viral long terminal
       repeats (LTRs). The results of gel filtration and a detailed binding
       density analysis indicate that the integrase binds to the LTR as a
       high-order oligomer at a density equivalent to 10 +/- 0.8 integrase
       monomers per 21-base pair LTR. The corresponding binding isotherm
       displays a Hill coefficient of 2, suggesting that the binding mechanism
       involves the cooperative interaction between two oligomers. This
       interaction is quite stable, exhibiting a prolonged half-life (t1/2
       approximately 13 h) in the presence of Mn2+ cations. Complexes were less
       stable when formed with Mg2+ (t1/2 approximately 1 h). The role of Mn2+
       appears to be in the induction of the protein-protein interactions that
       stabilize the bound complexes. In terms of the 3'-end processing of the
       LTR, similar catalytic rates (kcat approximately 0.06 min-1) were
       obtained for the stable complex in the presence of either cation. Hence,
       the apparent preference observed for Mn2+ in standard in vitro
       integration assays can be attributed entirely to the augmentation in the
       DNA binding affinity of the integrase.
 DE    Base Sequence  Binding Sites  Cations, Divalent/PHARMACOLOGY
       Comparative Study  DNA Nucleotidyltransferases/CHEMISTRY/ISOLATION &
       PURIF/  *METABOLISM  DNA, Viral/*METABOLISM  Human  *HIV Long Terminal
       Repeat  HIV-1/*ENZYMOLOGY/GENETICS  Kinetics  Magnesium/*PHARMACOLOGY
       Manganese/*PHARMACOLOGY  Mathematics  Models, Theoretical  Molecular
       Sequence Data  Oligodeoxyribonucleotides  Recombinant
       Proteins/CHEMISTRY/ISOLATION & PURIF/METABOLISM  Substrate Specificity
       Support, Non-U.S. Gov't  Time Factors  Virus Integration  JOURNAL
       ARTICLE

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