2-Oxo acid dehydrogenase multi-enzyme complexes: in the beginning and halfway there.
The lipoate acyltransferase components of the pyruvate and 2-oxoglutarate dehydrogenase complexes are highly segmented proteins, forming the structural and mechanistic cores of the complexes. Various functional domains can be isolated by controlled proteolysis, the cleavage sites occurring in conformationally flexible segments of polypeptide chain with unusual sequences. The complexes exhibit novel properties of active-site coupling, which stem from their unusual quaternary structure and the polypeptide chain flexibility that enables protein domains to move with respect to the three contributing active sites during catalysis. In vitro mutagenesis, high resolution n.m.r. spectroscopy and the methods of protein engineering are providing important insights into the mechanics of these processes, with more general implications for the design principles of macromolecular assemblies.
Perham
R N
RN
Department of Biochemistry, University of Cambridge, U.K.
Packman
L C
LC
Radford
S E
SE
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D001665:Binding Sites; D002952:Citric Acid Cycle; D004926:Escherichia coli / Q000201:enzymology; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D009097:Multienzyme Complexes; D010446:Peptide Fragments; D011768:Pyruvate Dehydrogenase Complex; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)