This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.




1dvm

From Proteopedia

Revision as of 14:30, 12 November 2007 by OCA (Talk | contribs)
(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)
Jump to: navigation, search
Image:1dvm.gif

1dvm, resolution 2.40Å

Drag the structure with the mouse to rotate

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 CL 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 Mon Nov 12 16:36:28 2007

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1dvm"
Personal tools