1CQP

CRYSTAL STRUCTURE ANALYSIS OF THE COMPLEX LFA-1 (CD11A) I-DOMAIN / LOVASTATIN AT 2.6 A RESOLUTION

1CQP の概要

• エントリーDOI: 10.2210/pdb1cqp/pdb
• 関連するPDBエントリー: 1LFA 1ZON 1ZOO 1ZOP
• 分子名称: ANTIGEN CD11A (P180), MAGNESIUM ION, LOVASTATIN, ... (4 entities in total)
• 機能のキーワード: rossmann fold, structural basis for lfa-1 inhibition, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P20701
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42499.41

構造登録者

Kallen, J.,Welzenbach, K.,Ramage, P.,Geyl, D.,Kriwacki, R.,Legge, G.,Cottens, S.,Weitz-Schmidt, G.,Hommel, U. (登録日: 1999-08-10, 公開日: 2000-08-07, 最終更新日: 2024-02-07)

主引用文献

Kallen, J.,Welzenbach, K.,Ramage, P.,Geyl, D.,Kriwacki, R.,Legge, G.,Cottens, S.,Weitz-Schmidt, G.,Hommel, U.
Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain.
J.Mol.Biol., 292:1-9, 1999

PubMed Abstract: The lymphocyte function-associated antigen (LFA-1) belongs to the family of beta2-integrins and plays an important role in T-cell activation and leukocyte migration to sites of inflammation. We report here that lovastatin, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor intercellular adhesion molecule-1. Using nuclear magnetic resonance spectroscopy and X-ray crystallography we show that the inhibitor binds to a highly conserved domain of the LFA-1 alpha-chain called the I-domain. The first three-dimensional structure of an integrin inhibitor bound to its receptor reveals atomic details for a hitherto unknown mode of LFA-1 inhibition. It also sheds light into possible mechanisms of LFA-1 mediated signalling and will support the design of novel anti-adhesive and immunosuppressive drugs.

PubMed: 10493852
DOI: 10.1006/jmbi.1999.3047

実験手法

X-RAY DIFFRACTION (2.6 Å)