9BXD

CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH HZ-IV-188

これはPDB形式変換不可エントリーです。

9BXD の概要

• エントリーDOI: 10.2210/pdb9bxd/pdb
• 分子名称: HIV-1 LM/HS clade A/E CRF01 gp120 core, 2-acetamido-2-deoxy-beta-D-glucopyranose, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (6 entities in total)
• 機能のキーワード: hiv-1 gp120, clade a/e cf01, viral protein
• 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: 42325.09

構造登録者

Niu, L.,Tolbert, W.D.,Pazgier, M. (登録日: 2024-05-22, 公開日: 2025-04-02)

主引用文献

Lee, D.,Niu, L.,Ding, S.,Zhu, H.,Tolbert, W.D.,Medjahed, H.,Beaudoin-Bussieres, G.,Abrams, C.,Finzi, A.,Pazgier, M.,Smith 3rd, A.B.
Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.
Acs Med.Chem.Lett., 15:1961-1969, 2024

PubMed Abstract: The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 protects infected cells from antibody-dependent cellular cytotoxicity (ADCC) by limiting the exposure of vulnerable epitopes to envelope glycoprotein (Env). Small-molecule CD4 mimetics (CD4mcs) based on piperidine scaffolds represent a new family of agents capable of sensitizing HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes on Env that are recognized by non-neutralizing antibodies which are abundant in plasma of people living with HIV. Here, we employed the combined methods of parallel synthesis, structure-based design, and optimization to generate a new line of piperidine-based CD4mcs, which sensitize HIV-1 infected cells to ADCC activity. The X-ray crystallographic study of the CD4mcs within the gp120 residues suggests that the positioning of the CD4mc inside the Phe43 cavity and synergistic contact of the CD4mc with the β loop and the α-helix lead to improved antiviral activity.

PubMed: 39563795
DOI: 10.1021/acsmedchemlett.4c00403

実験手法

X-RAY DIFFRACTION (1.85 Å)