3LW2

Mouse Plasminogen Activator Inhibitor-1 (PAI-1)

Summary for 3LW2

• Entry DOI: 10.2210/pdb3lw2/pdb
• Related: 1C5G 1DB2 1DVN 1LJ5 3EOX 9PAI
• Descriptor: Plasminogen activator inhibitor 1 (2 entities in total)
• Functional Keywords: latent mouse plasminogen activator inhibitor-1 (pai-1), glycoprotein, plasminogen activation, hydrolase inhibitor
• Biological source: Mus musculus (mouse)
• Cellular location: Secreted: P22777
• Total number of polymer chains: 1
• Total formula weight: 42795.99

Authors

Dewilde, M.,Van De Craen, B.,Compernolle, G.,Madsen, J.B.,Strelkov, S.V.,Gils, A.,Declerck, P.J. (deposition date: 2010-02-23, release date: 2010-04-07, Last modification date: 2023-09-06)

Primary citation

Dewilde, M.,Van De Craen, B.,Compernolle, G.,Madsen, J.B.,Strelkov, S.,Gils, A.,Declerck, P.J.
Subtle structural differences between human and mouse PAI-1 reveal the basis for biochemical differences.
J.Struct.Biol., 171:95-101, 2010

PubMed Abstract: Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that plays an important role in cardiovascular disorders and tumor development. The potential role of PAI-1 as a drug target has been evaluated in various animal models (e.g. mouse and rat). Sensitivity to PAI-1 inhibitory agents varied in different species. To date, absence of PAI-1 structures from species other than human hampers efforts to reveal the molecular basis for the observed species differences. Here we describe the structure of latent mouse PAI-1. Comparison with available structures of human PAI-1 reveals (1) a differential positioning of α-helix A; (2) differences in the gate region; and (3) differences in the reactive center loop position. We demonstrate that the optimal binding site of inhibitors may be dependent on the orthologs, and our results affect strategies in the rational design of a pharmacologically active PAI-1 inhibitor.

PubMed: 20230900
DOI: 10.1016/j.jsb.2010.03.006

Experimental method

X-RAY DIFFRACTION (1.93 Å)