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1: Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1832-7. Epub 2008 Feb 4.
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Structural identification of the pathway of long-range communication in an allosteric enzyme.

Gandhi PS, Chen Z, Mathews FS, Di Cera E.

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, St. Louis, MO 63110, USA.

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.

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PMID: 18250335 [PubMed - indexed for MEDLINE]

PMCID: PMC2538848