TY  - INPR
A1  - Kutter, Steffen
A1  - Weiss, Manfred S.
A1  - Wille, Georg
A1  - Golbik, Ralph
A1  - Spinka, Michael
A1  - König, Stephan
T1  - Covalently bound substrate at the regulatory site triggers allosteric enzyme activation
N2  - The mechanism by which the enzyme pyruvate decarboxylase from yeast is activated allosterically has been elucidated. A total of seven three-dimensional structures of the enzyme, of enzyme variants or of enzyme complexes from two yeast species (three of them reported here for the first time) provide detailed atomic resolution snapshots along the activation coordinate. The prime event is the covalent binding of the substrate pyruvate to the side chain of cysteine 221, thus forming a thiohemiketal. This reaction causes the shift of a neighbouring amino acid, which eventually leads to the rigidification of two otherwise flexible loops, where one of the loops provides two histidine residues necessary to complete the enzymatically competent active site architecture. The structural data are complemented and supported by kinetic investigations and binding studies and provide a consistent picture of the structural changes, which occur upon enzyme activation.
Y1  - 2008
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7146
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-71009
N1  - This document is licensed to the public under the Creative Commons Attribution 3.0 License http://creativecommons.org/licenses/by/3.0/
ER  -