4DVR

Crystal structure of YU2 gp120 core in complex with Fab 48d and NBD-557

4DVR の概要

• エントリーDOI: 10.2210/pdb4dvr/pdb
• 分子名称: Envelope glycoprotein gp120, Fab 48d Light chain, Fab 48d Heavy chain, ... (6 entities in total)
• 機能のキーワード: hiv-1 gp120, cd4 binding site, nbd-557, immune system-transcription inhibitor complex, immune system/transcription inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate YU-2) (HIV-1); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 83328.08

構造登録者

Kwon, Y.D.,Kwong, P.D. (登録日: 2012-02-23, 公開日: 2013-02-27, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)