6OOO

Crystal structure of HIV-1 LM/HT Clade A/E CRF01 gp120 core in complex with (S)-MCG-IV-226.

6OOO の概要

• エントリーDOI: 10.2210/pdb6ooo/pdb
• 分子名称: HIV-1 LM/HT Clade A/E CRF01 gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose, (3S,5R)-5-amino-N~3~-(4-chloro-3-fluorophenyl)-N~1~-propylpiperidine-1,3-dicarboxamide, ... (5 entities in total)
• 機能のキーワード: hiv-1 gp120, clade a/e cf01, viral protein, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42273.96

構造登録者

Tolbert, W.D.,Sherburn, R.,Pazgier, M. (登録日: 2019-04-23, 公開日: 2020-03-11, 最終更新日: 2024-11-13)

主引用文献

Grenier, M.C.,Ding, S.,Vezina, D.,Chapleau, J.P.,Tolbert, W.D.,Sherburn, R.,Schon, A.,Somisetti, S.,Abrams, C.F.,Pazgier, M.,Finzi, A.,Smith 3rd, A.B.
Optimization of Small Molecules That Sensitize HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.
Acs Med.Chem.Lett., 11:371-378, 2020

PubMed Abstract: With approximately 37 million people living with HIV worldwide and an estimated 2 million new infections reported each year, the need to derive novel strategies aimed at eradicating HIV-1 infection remains a critical worldwide challenge. One potential strategy would involve eliminating infected cells via antibody-dependent cellular cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to conceal epitopes located in its envelope glycoprotein (Env) that are recognized by ADCC-mediating antibodies present in sera from HIV-1 infected individuals. Our aim is to circumvent this evasion via the development of small molecules that expose relevant anti-Env epitopes and sensitize HIV-1 infected cells to ADCC. Rapid elaboration of an initial screening hit using parallel synthesis and structure-based optimization has led to the development of potent small molecules that elicit this humoral response. Efforts to increase the ADCC activity of this class of small molecules with the aim of increasing their therapeutic potential was based on our recent cocrystal structures with gp120 core.

PubMed: 32184972
DOI: 10.1021/acsmedchemlett.9b00445

実験手法

X-RAY DIFFRACTION (2.4 Å)