A Molecular Switch and Proton Wire Synchronize the Active Sites in Thiamine Enzymes
Copyright policy )A Molecular Switch and Proton Wire Synchronize the Active Sites in Thiamine Enzymes
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.
- University of Cambridge United Kingdom
Models, Molecular, Protein Folding, Binding Sites, Protein Conformation, Pyruvate Dehydrogenase Complex, Hydrogen-Ion Concentration, Crystallography, X-Ray, Dihydrolipoyllysine-Residue Acetyltransferase, Catalysis, Protein Structure, Tertiary, Geobacillus stearothermophilus, Kinetics, Protein Subunits, Amino Acid Substitution, Mutation, Pyruvate Dehydrogenase (Lipoamide), Phosphorylation, Protons, Protein Structure, Quaternary, Hydrophobic and Hydrophilic Interactions
Models, Molecular, Protein Folding, Binding Sites, Protein Conformation, Pyruvate Dehydrogenase Complex, Hydrogen-Ion Concentration, Crystallography, X-Ray, Dihydrolipoyllysine-Residue Acetyltransferase, Catalysis, Protein Structure, Tertiary, Geobacillus stearothermophilus, Kinetics, Protein Subunits, Amino Acid Substitution, Mutation, Pyruvate Dehydrogenase (Lipoamide), Phosphorylation, Protons, Protein Structure, Quaternary, Hydrophobic and Hydrophilic Interactions
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