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1dvn

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{{STRUCTURE_1dvn| PDB=1dvn | SCENE= }}
{{STRUCTURE_1dvn| PDB=1dvn | SCENE= }}
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'''LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)'''
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===LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)===
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==Overview==
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Serpins exhibit a range of physiological roles and can contribute to certain disease states dependent on their various conformations. Understanding the mechanisms of the large-scale conformational reorganizations of serpins may lead to a better understanding of their roles in various cardiovascular diseases. We have studied the serpin, plasminogen activator inhibitor 1 (PAI-1), in both the active and the latent state and found that anionic halide ions may play a role in the active-to-latent structural transition. Crystallographic analysis of a stable mutant form of active PAI-1 identified an anion-binding site between the central beta-sheet and a small surface domain. A chloride ion was modeled in this site, and its identity was confirmed by soaking crystals in a bromide-containing solution and calculating a crystallographic difference map. The anion thus located forms a 4-fold ligated linchpin that tethers the surface domain to the central beta-sheet into which the reactive center loop must insert during the active-to-latent transition. Timecourse experiments measuring active PAI-1 stability in the presence of various halide ions showed a clear trend for stabilization of the active form with F(-) &gt; Cl(-) &gt; Br(-) &gt;&gt; I(-). We propose that the "stickiness" of this pin (i.e., the electronegativity of the anion) contributes to the energetics of the active-to-latent transition in the PAI-1 serpin.
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==About this Structure==
==About this Structure==
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[[Category: Pai-1]]
[[Category: Pai-1]]
[[Category: Serpin]]
[[Category: Serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:20:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:41:18 2008''

Revision as of 20:41, 30 June 2008

Template:STRUCTURE 1dvn

LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)

Template:ABSTRACT PUBMED 10913251

About this Structure

1DVN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structures of active and latent PAI-1: a possible stabilizing role for chloride ions., Stout TJ, Graham H, Buckley DI, Matthews DJ, Biochemistry. 2000 Jul 25;39(29):8460-9. PMID:10913251

Page seeded by OCA on Mon Jun 30 23:41:18 2008

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