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1dvm
From Proteopedia
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'''ACTIVE FORM OF HUMAN PAI-1''' | '''ACTIVE FORM OF HUMAN PAI-1''' | ||
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[[Category: Matthews, D J.]] | [[Category: Matthews, D J.]] | ||
[[Category: Stout, T J.]] | [[Category: Stout, T J.]] | ||
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Revision as of 11:20, 2 May 2008
ACTIVE FORM OF HUMAN PAI-1
Overview
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(-) > Cl(-) > Br(-) >> 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.
About this Structure
1DVM 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 Fri May 2 14:20:09 2008
Categories: Homo sapiens | Single protein | Buckley, D I. | Graham, H. | Matthews, D J. | Stout, T J. | Inhibitor | Pai-1 | Serpin
