3BEI

Crystal structure of the slow form of thrombin in a self_inhibited conformation

Summary for 3BEI

• Entry DOI: 10.2210/pdb3bei/pdb
• Related: 2GP9 3BEF
• Descriptor: Prothrombin, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• Functional Keywords: serine protease, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, secreted, zymogen
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 35336.33

Authors

Gandhi, P.S.,Chen, Z.,Mathews, F.S.,Di Cera, E. (deposition date: 2007-11-19, release date: 2007-12-25, Last modification date: 2024-10-16)

Primary citation

Gandhi, P.S.,Chen, Z.,Mathews, F.S.,Di Cera, E.
Structural identification of the pathway of long-range communication in an allosteric enzyme.
Proc.Natl.Acad.Sci.Usa, 105:1832-1837, 2008

PubMed Abstract: 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.

PubMed: 18250335
DOI: 10.1073/pnas.0710894105

Experimental method

X-RAY DIFFRACTION (1.55 Å)