1dvn
From Proteopedia
(New page: 200px<br /> <applet load="1dvn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dvn, resolution 2.10Å" /> '''LATENT FORM OF PLAS...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1dvn. | + | [[Image:1dvn.jpg|left|200px]]<br /><applet load="1dvn" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dvn" size=" | + | |
caption="1dvn, resolution 2.10Å" /> | caption="1dvn, resolution 2.10Å" /> | ||
'''LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)'''<br /> | '''LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)'''<br /> | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1DVN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1DVN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DVN OCA]. |
==Reference== | ==Reference== | ||
| Line 25: | Line 24: | ||
[[Category: serpin]] | [[Category: serpin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:40:59 2008'' |
Revision as of 13:40, 15 February 2008
|
LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (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
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 Fri Feb 15 15:40:59 2008
Categories: Homo sapiens | Single protein | Buckley, D.I. | Graham, H. | Matthews, D.J. | Stout, T.J. | Inhibitor | Pai-1 | Serpin
