1w85

Publication Abstract from PubMed

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.

A molecular switch and proton wire synchronize the active sites in thiamine enzymes.,Frank RA, Titman CM, Pratap JV, Luisi BF, Perham RN Science. 2004 Oct 29;306(5697):872-6. PMID:15514159^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.