Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain.

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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. 1999 Sep 10;292(1):1-9.

PubMed ID

10493852 [ View in 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Lovastatin	Integrin alpha-L	Protein	Humans	Unknown	Inhibitor	Details

Polypeptides

Name	UniProt ID
Integrin alpha-L	P20701	Details