The structure of an HIV-1 specific cell entry inhibitor in complex with the HIV-1 gp41 trimeric core |
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Authors: | Zhou G Ferrer M Chopra R Kapoor T M Strassmaier T Weissenhorn W Skehel J J Oprian D Schreiber S L Harrison S C Wiley D C |
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Affiliation: | Laboratory of Molecular Medicine, The Children's Hospital, Boston, MA 02115, USA. |
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Abstract: | 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. |
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