In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 6 ( 2008-02-12), p. 1832-1837
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0710894105
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2008
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
