Crystal structure of the HIV-1 integrase core domain in complex with sucrose reveals details of an allosteric inhibitory binding site

FEBS Lett. 2010 Apr 16;584(8):1455-62. doi: 10.1016/j.febslet.2010.03.016. Epub 2010 Mar 16.

Abstract

HIV integrase (IN) is an essential enzyme in HIV replication and an important target for drug design. IN has been shown to interact with a number of cellular and viral proteins during the integration process. Disruption of these important interactions could provide a mechanism for allosteric inhibition of IN. We present the highest resolution crystal structure of the IN core domain to date. We also present a crystal structure of the IN core domain in complex with sucrose which is bound at the dimer interface in a region that has previously been reported to bind integrase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Allosteric Regulation
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Discovery
  • Glycerol / metabolism
  • HIV Integrase / chemistry*
  • HIV Integrase / genetics
  • HIV Integrase / isolation & purification
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / metabolism*
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-1 / physiology
  • Models, Molecular
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sucrose / metabolism*
  • Virus Replication / drug effects

Substances

  • HIV Integrase Inhibitors
  • Sucrose
  • HIV Integrase
  • Glycerol