1CQP

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

Summary for 1CQP

• Entry DOI: 10.2210/pdb1cqp/pdb
• Related: 1LFA 1ZON 1ZOO 1ZOP
• Descriptor: ANTIGEN CD11A (P180), MAGNESIUM ION, LOVASTATIN, ... (4 entities in total)
• Functional Keywords: rossmann fold, structural basis for lfa-1 inhibition, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P20701
• Total number of polymer chains: 2
• Total formula weight: 42499.41

Authors

Kallen, J.,Welzenbach, K.,Ramage, P.,Geyl, D.,Kriwacki, R.,Legge, G.,Cottens, S.,Weitz-Schmidt, G.,Hommel, U. (deposition date: 1999-08-10, release date: 2000-08-07, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)