Publication Date:
2004-10-30
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frank, Rene A W -- Titman, Christopher M -- Pratap, J Venkatesh -- Luisi, Ben F -- Perham, Richard N -- New York, N.Y. -- Science. 2004 Oct 29;306(5697):872-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15514159" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Substitution
;
Binding Sites
;
Catalysis
;
Crystallography, X-Ray
;
Dihydrolipoyllysine-Residue Acetyltransferase
;
Geobacillus stearothermophilus/*enzymology
;
Hydrogen-Ion Concentration
;
Hydrophobic and Hydrophilic Interactions
;
Kinetics
;
Models, Molecular
;
Mutation
;
Phosphorylation
;
Protein Conformation
;
Protein Folding
;
Protein Structure, Quaternary
;
Protein Structure, Tertiary
;
Protein Subunits/chemistry/metabolism
;
Protons
;
Pyruvate Dehydrogenase (Lipoamide)/*chemistry/genetics/*metabolism
;
Pyruvate Dehydrogenase Complex/*chemistry/*metabolism
;
Pyruvic Acid/metabolism
;
Thiamine Pyrophosphate/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
