4rz8 | pdb_00004rz8

Crystal structure of HIV-1 gp120 core in complex with NBD-11021, a small molecule CD4-antagonist

spinqualitylabelsall models 4rz8, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rz8 is a 4 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 3ZM, EPE, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0M3KKW9_9HIV1 Publication Abstract from PubMed Earlier we reported the discovery and design of NBD-556 and their analogs which demonstrated their potential as HIV-1 entry inhibitors. However, progress in developing these inhibitors has been stymied by their CD4-agonist properties, an unfavorable trait for use as drug. Here, we demonstrate the successful conversion of a full CD4-agonist (NBD-556) through a partial CD4-agonist (NBD-09027), to a full CD4-antagonist (NBD-11021) by structure-based modification of the critical oxalamide midregion, previously thought to be intolerant of modification. NBD-11021 showed unprecedented neutralization breath for this class of inhibitors, with pan-neutralization against a panel of 56 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates (IC50 as low as 270 nM). The cocrystal structure of NBD-11021 complexed to a monomeric HIV-1 gp120 core revealed its detail binding characteristics. The study is expected to provide a framework for further development of NBD series as HIV-1 entry inhibitors for clinical application against AIDS. Structure-Based Design of a Small Molecule CD4-Antagonist with Broad Spectrum Anti-HIV-1 Activity.,Curreli F, Kwon YD, Zhang H, Scacalossi D, Belov DS, Tikhonov AA, Andreev IA, Altieri A, Kurkin AV, Kwong PD, Debnath AK J Med Chem. 2015 Aug 28. PMID:26301736 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gp120 3D structures

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