Induction of a nonproductive conformational change in gp120 by a small molecule HIV type 1 entry inhibitor.

Journal Article (Journal Article)

Conformational changes in HIV-1 envelope glycoproteins, gp120 and gp41, is a dynamic process essential for HIV-1 entry. Here we show that a small molecule HIV-1 entry inhibitor, IC9564, induces a conformational change in gp120. The conformational change in gp120 is evidenced by a significant increase in the binding of a conformational monoclonal antibody 17b. As a result of the conformational effect, IC9564 significantly enhances the neutralizing activity of 17b. Unlike CD4, IC9564 does not trigger conformational changes in gp41. In fact, IC9564 inhibits CD4-induced conformational changes in gp41. Thus, IC9564 exploits the dynamic nature of gp120 by inducing a nonproductive gp120 conformation that is not able to trigger a conformational change in gp41 for membrane fusion.

Full Text

Duke Authors

Cited Authors

  • Huang, L; Lai, W; Ho, P; Chen, CH

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 28 - 32

PubMed ID

  • 17263629

International Standard Serial Number (ISSN)

  • 0889-2229

Digital Object Identifier (DOI)

  • 10.1089/aid.2006.0137


  • eng

Conference Location

  • United States