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PDBsum entry 3lw2
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Hydrolase inhibitor
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PDB id
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3lw2
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References listed in PDB file
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Key reference
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Title
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Subtle structural differences between human and mouse pai-1 reveal the basis for biochemical differences.
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Authors
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M.Dewilde,
B.Van de craen,
G.Compernolle,
J.B.Madsen,
S.Strelkov,
A.Gils,
P.J.Declerck.
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Ref.
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J Struct Biol, 2010,
171,
95.
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PubMed id
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Abstract
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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 alpha-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.
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