title: The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M tuberculosis.
abstract: Ketopantoate hydroxymethyltransferase (KPHMT) catalyzes the first committed step in the biosynthesis of pantothenate, which is a precursor to coenzyme A and is required for penicillin biosynthesis. The crystal structure of KPHMT from Mycobacterium tuberculosis was determined by the single anomalous substitution (SAS) method at 2.8 A resolution. KPHMT adopts a structure that is a variation on the (beta/alpha) barrel fold, with a metal binding site proximal to the presumed catalytic site. The protein forms a decameric complex, with subunits in opposing pentameric rings held together by a swapping of their C-terminal alpha helices. The structure reveals KPHMT's membership in a small, recently discovered group of (beta/alpha) barrel enzymes that employ domain swapping to form a variety of oligomeric assemblies. The apparent conservation of certain detailed structural characteristics suggests that KPHMT is distantly related by divergent evolution to enzymes in unrelated pathways, including isocitrate lyase and phosphoenolpyruvate mutase.
authors.affiliation: UCLA Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Barnali N
authors.initials: BN
authors.lastname: Chaudhuri
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.forename: Chang Yub
authors.initials: CY
authors.lastname: Kim
authors.forename: Geoff S
authors.initials: GS
authors.lastname: Waldo
authors.forename: Min S
authors.initials: MS
authors.lastname: Park
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Terwilliger
authors.forename: Todd O
authors.initials: TO
authors.lastname: Yeates
mesh_terms: D001665:Binding Sites; D019877:Hydroxymethyl and Formyl Transferases / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010205:Pantothenic Acid / Q000096:biosynthesis*; D011487:Protein Conformation
chemical_list: D010205:Pantothenic Acid; D019877:Hydroxymethyl and Formyl Transferases; C021477:3-methyl-2-oxobutanoate hydroxymethyltransferase