6UT1

CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH BNM-III-170

6UT1 の概要

• エントリーDOI: 10.2210/pdb6ut1/pdb
• 分子名称: HIV-1 LM/HS clade A/E CRF01 gp120 core, 2-acetamido-2-deoxy-beta-D-glucopyranose, ~{N}'-[(1~{R},2~{R})-2-(carbamimidamidomethyl)-5-(methylaminomethyl)-2,3-dihydro-1~{H}-inden-1-yl]-~{N}-(4-chloranyl-3-fluoranyl-phenyl)ethanediamide, ... (5 entities in total)
• 機能のキーワード: hiv-1 gp120, clade a/e cf01, viral protein, immune system
• 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: 42350.01

構造登録者

Tolbert, W.D.,Sherburn, R.,Pazgier, M. (登録日: 2019-10-29, 公開日: 2020-10-07, 最終更新日: 2024-11-06)

主引用文献

Prevost, J.,Tolbert, W.D.,Medjahed, H.,Sherburn, R.T.,Madani, N.,Zoubchenok, D.,Gendron-Lepage, G.,Gaffney, A.E.,Grenier, M.C.,Kirk, S.,Vergara, N.,Han, C.,Mann, B.T.,Chenine, A.L.,Ahmed, A.,Chaiken, I.,Kirchhoff, F.,Hahn, B.H.,Haim, H.,Abrams, C.F.,Smith 3rd, A.B.,Sodroski, J.,Pazgier, M.,Finzi, A.
The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site.
Mbio, 11:-, 2020

PubMed Abstract: The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity ("the Phe43 cavity") located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc. The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics.

PubMed: 32457241
DOI: 10.1128/mBio.00280-20

実験手法

X-RAY DIFFRACTION (2.65 Å)