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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)'''
| | ===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(-) > 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10913251}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10913251 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10913251}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Pai-1]] | | [[Category: Pai-1]] |
| [[Category: Serpin]] | | [[Category: Serpin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:20:08 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:41:18 2008'' |
