Paper: Structural identification of the pathway of long-range communication in an allosteric enzyme

Gandhi PS, Chen Z, Mathews FS, Di Cera E.  Structural identification of the pathway of long-range communication in an allosteric enzyme.  Proc Natl Acad Sci, 105 (6):  1832-7, 2008.

http://10.1073/pnas.0710894105

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 β-strand. Binding of a fragment of the protease activated receptor PAR1 to exosite I, 30-Å away from the active site region, causes a large conformational change that corrects the position of the 215–219 β-strand and restores access to the active site. The crystal structure of the thrombin-PAR1 complex, solved at 2.2-Å resolution, reveals the details of this long-range allosteric communication in terms of a network of polar interactions.