PDBsum entry 3cvm

Blood clotting

PDB id: 3cvm

Contents

Protein chain

377 a.a. *

Waters ×810

* Residue conservation analysis

PDB id:

3cvm

Name:

Blood clotting

Title:

High resolution structure of a stable plasminogen activator inhibitor type-1 in its protease cleaved form

Structure:

Plasminogen activator inhibitor 1. Chain: a, b. Synonym: pai-1, endothelial plasminogen activator inhibitor, pai. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Gene: serpine1, pai1, planh1. Expressed in: escherichia coli.

Resolution:

2.02Å R-factor: 0.229 R-free: 0.282

Authors:

J.K.Jensen,P.G.W.Gettins

Key ref:

J.K.Jensen and P.G.Gettins (2008). High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling. Protein Sci, 17, 1844-1849. PubMed id: 18725454 DOI: 10.1110/ps.036707.108

Date:

18-Apr-08 Release date: 19-Aug-08

Protein chains

P05121  (PAI1_HUMAN) -  Plasminogen activator inhibitor 1 from Homo sapiens

Seq: 402 a.a.

Struc: 377 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1110/ps.036707.108

Protein Sci 17:1844-1849 (2008)

PubMed id: 18725454

High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling.

J.K.Jensen, P.G.Gettins.

ABSTRACT

Wild-type plasminogen activator inhibitor type-1 (PAI-1) rapidly converts to the inactive latent state under conditions of physiological pH and temperature. For in vivo studies of active PAI-1 in cell culture and in vivo model systems, the 14-1B PAI-1 mutant (N150H-K154T-Q319L-M354I), with its stabilized active conformation, has thus become the PAI-1 of choice. As a consequence of the increased stability, the only two forms likely to be encountered are the active or the cleaved form, the latter either free or complexed with target proteinase. We hereby report the first structure of the stable 14-1B PAI-1 variant in its reactive center cleaved form, to a resolution of 2.0 A. The >99% complete structure represents the highest resolved structure of free cleaved PAI-1. This high-resolution structure should be of great use for drug target development and for modeling protein-protein interactions such as those of PAI-1 with vitronectin.

Selected figure(s)

Figure 3.
Figure 3. Close-up comparison of the ligand-binding cavity in the flexible joints region of active 14-1B (1DVM) and rcc14-B (3CVM, present structure). (A) Active 14-1B; (B) cleaved 14-1B. The cavity boundaries are outlined by broken lines. Residues surrounding the cavity are labeled.

The above figure is reprinted by permission from the Protein Society: Protein Sci (2008, 17, 1844-1849) copyright 2008.

Figure was selected by an automated process.