4dko | pdb_00004dko

Crystal structure of clade A/E 93TH057 HIV-1 gp120 core in complex with TS-II-224

spinqualitylabelsall models 4dko, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4dko is a 2 chain structure with sequence from Hiv-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0LM, EPE, NAG Related: 4dkp, 4dkq, 4dkr Gene: HIV-1 Env (HIV-1) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Cellular infection by HIV-1 is initiated with a binding event between the viral envelope glycoprotein gp120 and the cellular receptor protein CD4. The CD4-gp120 interface is dominated by two hotspots: a hydrophobic gp120 cavity capped by Phe43(CD4) and an electrostatic interaction between residues Arg59(CD4) and Asp368(gp120). The CD4 mimetic small-molecule NBD-556 (1) binds within the gp120 cavity; however, 1 and related congeners demonstrate limited viral neutralization breadth. Herein, we report the design, synthesis, characterization, and X-ray structures of gp120 in complex with small molecules that simultaneously engage both binding hotspots. The compounds specifically inhibit viral infection of 42 tier 2 clades B and C viruses and are shown to be antagonists of entry into CD4-negative cells. Dual hotspot design thus provides both a means to enhance neutralization potency of HIV-1 entry inhibitors and a novel structural paradigm for inhibiting the CD4-gp120 protein-protein interaction. Structure-Based Design, Synthesis, and Characterization of Dual Hotspot Small-Molecule HIV-1 Entry Inhibitors.,Lalonde JM, Kwon YD, Jones DM, Sun AW, Courter JR, Soeta T, Kobayashi T, Princiotto AM, Wu X, Schon A, Freire E, Kwong PD, Mascola JR, Sodroski J, Madani N, Smith AB 3rd J Med Chem. 2012 Apr 23. PMID:22497421 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gp120

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