1dvm
From Proteopedia
(New page: 200px<br /> <applet load="1dvm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dvm, resolution 2.40Å" /> '''ACTIVE FORM OF HUMA...) |
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| - | [[Image:1dvm.gif|left|200px]]<br /> | + | [[Image:1dvm.gif|left|200px]]<br /><applet load="1dvm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dvm" size=" | + | |
caption="1dvm, resolution 2.40Å" /> | caption="1dvm, resolution 2.40Å" /> | ||
'''ACTIVE FORM OF HUMAN PAI-1'''<br /> | '''ACTIVE FORM OF HUMAN PAI-1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Serpins exhibit a range of physiological roles and can contribute to | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DVM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1DVM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DVM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Buckley, D | + | [[Category: Buckley, D I.]] |
[[Category: Graham, H.]] | [[Category: Graham, H.]] | ||
| - | [[Category: Matthews, D | + | [[Category: Matthews, D J.]] |
| - | [[Category: Stout, T | + | [[Category: Stout, T J.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
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[[Category: serpin]] | [[Category: serpin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:57 2008'' |
Revision as of 10:21, 21 February 2008
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ACTIVE FORM OF HUMAN PAI-1
Contents |
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.
Disease
Known diseases associated with this structure: Hemorrhagic diathesis due to PAI1 deficiency OMIM:[173360], Thrombophilia due to excessive plasminogen activator inhibitor OMIM:[173360]
About this Structure
1DVM is a Single protein structure of sequence from Homo sapiens with as ligand. 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 Thu Feb 21 12:20:57 2008
Categories: Homo sapiens | Single protein | Buckley, D I. | Graham, H. | Matthews, D J. | Stout, T J. | CL | Inhibitor | Pai-1 | Serpin
