Multiple modes of active center communication in thiamin diphosphate-dependent enzymes.
Detection of interaction between cofactors at the active centers of homodimeric and homotetrameric enzymes is usually elusive by steady-state kinetic approaches and requires protein variants where such interactions are diminished or exaggerated. In this Account, evidence for active-center interactions will be presented for the following thiamin diphosphate-dependent enzymes: yeast pyruvate decarboxylase, benzoylformate decarboxylase, and examples from the 2-oxoacid dehydrogenase multienzyme complex class. The dissymmetry of active sites is especially evident in the X-ray structures of these enzymes with substrate/substrate analogues bound. Perturbations that reveal active center communication include use of chromophoric substrates and substitutions of active center residues on putative pathways.
Jordan
Frank
F
Department of Chemistry, Rutgers, the State University of New Jersey, Newark, New Jersey 07102, USA.
Nemeria
Natalia S
NS
Sergienko
Eduard
E
D001665:Binding Sites; D002262:Carboxy-Lyases / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D007658:Ketone Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D011767:Pyruvate Decarboxylase / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013835:Thiamine Pyrophosphate / Q000737:chemistry*; D015003:Yeasts / Q000201:enzymology
D009097:Multienzyme Complexes; D007658:Ketone Oxidoreductases; D002262:Carboxy-Lyases; D011767:Pyruvate Decarboxylase; C019778:benzoylformate decarboxylase; D013835:Thiamine Pyrophosphate