Comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily.
Escherichia coli ketopantoate hydroxymethyltransferase (KPHMT) catalyzes the first step in the biosynthesis pathway of pantothenate (vitamin B(5)), the transfer of a hydroxymethyl group onto alpha-ketoisovalerate. Here we describe a detailed comparative analysis of the KPHMT crystal structure and the identification of structural homologues, some of which have remarkable similarities in their active sites, modes of binding to substrates, and mechanisms. We show that KPHMT forms a family within the phosphoenolpyruvate/pyruvate superfamily. Based on the analysis, we propose that in this superfamily there should be a subdivision into two groups. This paper completes our structural analysis of the E. coli enzymes in the pantothenate pathway.
Schmitzberger
Florian
F
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Smith
Alison G
AG
Abell
Chris
C
Blundell
Tom L
TL
D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D019877:Hydroxymethyl and Formyl Transferases / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D007522:Isocitrate Lyase / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010728:Phosphoenolpyruvate / Q000378:metabolism*; D017875:Phosphotransferases (Phosphomutases) / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D019289:Pyruvic Acid / Q000378:metabolism*
D010728:Phosphoenolpyruvate; D019289:Pyruvic Acid; D019877:Hydroxymethyl and Formyl Transferases; C021477:3-methyl-2-oxobutanoate hydroxymethyltransferase; D007522:Isocitrate Lyase; D017875:Phosphotransferases (Phosphomutases); C057167:phosphoenolpyruvate mutase