A Molecular Switch and Proton Wire Synchronize the Active Sites in Thiamine Enzymes
- 29 October 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 306 (5697) , 872-876
- https://doi.org/10.1126/science.1101030
Abstract
Thiamine diphosphate (ThDP) is used as a cofactor in many key metabolic enzymes. We present evidence that the ThDPs in the two active sites of the E1 (EC 1.2.4.1) component of the pyruvate dehydrogenase complex communicate over a distance of 20 angstroms by reversibly shuttling a proton through an acidic tunnel in the protein. This “proton wire” permits the co-factors to serve reciprocally as general acid/base in catalysis and to switch the conformation of crucial active-site peptide loops. This synchronizes the progression of chemical events and can account for the oligomeric organization, conformational asymmetry, and “ping-pong” kinetic properties of E1 and other thiamine-dependent enzymes.Keywords
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