3bef

File:3bef.jpg

Crystal structure of thrombin bound to the extracellular fragment of PAR1

OverviewOverview

Allostery is a common mechanism of regulation of enzyme activity and specificity, and its signatures are readily identified from functional studies. For many allosteric systems, structural evidence exists of long-range communication among protein domains, but rarely has this communication been traced to a detailed pathway. The thrombin mutant D102N is stabilized in a self-inhibited conformation where access to the active site is occluded by a collapse of the entire 215-219 beta-strand. Binding of a fragment of the protease activated receptor PAR1 to exosite I, 30-A away from the active site region, causes a large conformational change that corrects the position of the 215-219 beta-strand and restores access to the active site. The crystal structure of the thrombin-PAR1 complex, solved at 2.2-A resolution, reveals the details of this long-range allosteric communication in terms of a network of polar interactions.

DiseaseDisease

Known disease associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this StructureAbout this Structure

3BEF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural identification of the pathway of long-range communication in an allosteric enzyme., Gandhi PS, Chen Z, Mathews FS, Di Cera E, Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1832-7. Epub 2008 Feb 4. PMID:18250335 Page seeded by OCA on Wed Apr 30 13:37:37 2008