National Center for
1FAV: The Structure Of An Hiv-1 Specific Cell Entry Inhibitor In Complex With The Hiv-1 Gp41 Trimeric Core
The structure of an HIV-1 specific cell entry inhibitor in complex with the HIV-1 gp41 trimeric core
Bioorg. Med. Chem. (2000) 8 p.2219-2227
The three-dimensional structure of the complex between an HIV-1 cell-entry inhibitor selected from screening a combinatorial library of non-natural building blocks and the central, trimeric, coiled-coil core of HIV-1 gp41 has been determined by X-ray crystallography. The biased combinatorial library was designed to identify ligands binding in nonpolar pockets on the surface of the coiled-coil core of gp41. The crystal structure shows that the non-peptide moiety of the inhibitor binds to the targeted cavity in two different binding modes. This result suggests a strategy for increasing inhibitor potency by use of a second-generation combinatorial library designed to give simultaneous occupancy of both binding sites.