4DVX

Crystal structure of clade A/E 93TH057 HIV-1 gp120 core in complex with MAE-II-188

Summary for 4DVX

• Entry DOI: 10.2210/pdb4dvx/pdb
• Related: 4DVR 4DVS 4DVT 4DVU 4DVV 4DVW
• Descriptor: clade A/E 93TH057 HIV-1 gp120 core, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-(4-chloro-3-fluorophenyl)-N'-{[(3R)-1-cyclopropylpyrrolidin-3-yl]methyl}ethanediamide, ... (5 entities in total)
• Functional Keywords: hiv-1 gp120, small molecule inhibitor, cd4 binding site, mae-ii-188, viral protein-transcription inhibitor complex, viral protein/transcription inhibitor
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 84343.50

Authors

Kwon, Y.D.,Kwong, P.D. (deposition date: 2012-02-23, release date: 2013-02-27, Last modification date: 2024-10-16)

Primary citation

Kwon, Y.D.,Lalonde, J.M.,Yang, Y.,Elban, M.A.,Sugawara, A.,Courter, J.R.,Jones, D.M.,Smith, A.B.,Debnath, A.K.,Kwong, P.D.
Crystal Structures of HIV-1 gp120 Envelope Glycoprotein in Complex with NBD Analogues That Target the CD4-Binding Site.
Plos One, 9:e85940-e85940, 2014

PubMed Abstract: Efforts to develop therapeutic agents that inhibit HIV-1 entry have led to the identification of several small molecule leads. One of the most promising is the NBD series, which binds within a conserved gp120 cavity and possesses para-halogen substituted aromatic rings, a central oxalamide linker, and a tetramethylpiperidine moiety. In this study, we characterized structurally the interactions of four NBD analogues containing meta-fluoro substitution on the aromatic ring and various heterocyclic ring replacements of the tetramethylpiperidine group. The addition of a meta-fluorine to the aromatic ring improved surface complementarity and did not alter the position of the analogue relative to gp120. By contrast, heterocyclic ring replacements of the tetramethylpiperidine moiety exhibited diverse positioning and interactions with the vestibule of the gp120 cavity. Overall, the biological profile of NBD-congeners was modulated by ligand interactions with the gp120-cavity vestibule. Herein, six co-crystal structures of NBD-analogues with gp120 provide a structural framework for continued small molecule-entry inhibitor optimization.

PubMed: 24489681
DOI: 10.1371/journal.pone.0085940

Experimental method

X-RAY DIFFRACTION (2.4 Å)