title: Restructuring catalysis in the mandelate pathway.
abstract: Mandelate racemase (MR) is the first enzyme in the bacterial pathway that converts mandelic acid to benzoic acid. The mandelate pathway can utilize either enantiomer of mandelate because this enzyme interconverts them. We have solved the structure of MR at 2.5 A resolution. The enzyme is almost identical in conformation to another bacterial enzyme, muconate lactonizing enzyme (MLE). Both enzymes are TIM-barrel proteins. This result has profound implications for the evolution of enzymic function and the origin of metabolic pathways. It also implies that it should be possible to transform one enzyme into the other by site-directed mutagenesis.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: D C
authors.initials: DC
authors.lastname: Neidhart
authors.forename: P L
authors.initials: PL
authors.lastname: Howell
authors.forename: G A
authors.initials: GA
authors.lastname: Petsko
authors.forename: J A
authors.initials: JA
authors.lastname: Gerlt
authors.forename: J W
authors.initials: JW
authors.lastname: Kozarich
authors.forename: V M
authors.initials: VM
authors.lastname: Powers
authors.forename: G L
authors.initials: GL
authors.lastname: Kenyon
mesh_terms: D002384:Catalysis; D019753:Intramolecular Lyases; D007535:Isomerases / Q000378:metabolism; D008333:Mandelic Acids / Q000378:metabolism*; D015394:Molecular Structure; D011487:Protein Conformation; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism
chemical_list: D008333:Mandelic Acids; D007535:Isomerases; D019998:Racemases and Epimerases; C021540:mandelate racemase; D019753:Intramolecular Lyases; C021811:muconate cycloisomerase; C037938:mandelic acid