title: Mandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous.
abstract: Mandelate racemase (MR) and muconate lactonizing enzyme (MLE) catalyse separate and mechanistically distinct reactions necessary for the catabolism of aromatic acids by Pseudomonas putida. The X-ray crystal structure of MR, solved at 2.5 A resolution, reveals that the secondary, tertiary and quaternary structures of MR and MLE are remarkably similar; also, MR and MLE are about 26% identical in primary structure. However, MR has no detectable MLE activity and vice versa. Thus, MR and MLE constitute the first example of enzymes that catalyse different reactions, as opposed to mechanistically identical reactions on different substrates, yet possess sufficient structural and sequence identity that they are likely to have evolved from a common ancestor. The discovery that MR and MLE catalyse different reactions but share a common structural framework has broad implications for the natural evolution of enzymes and metabolic pathways, as well as for the rational modification of enzyme activities.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: D J
authors.initials: DJ
authors.lastname: Neidhart
authors.forename: G L
authors.initials: GL
authors.lastname: Kenyon
authors.forename: J A
authors.initials: JA
authors.lastname: Gerlt
authors.forename: G A
authors.initials: GA
authors.lastname: Petsko
mesh_terms: D001665:Binding Sites; D005075:Biological Evolution; D002384:Catalysis; D003460:Crystallization; D019753:Intramolecular Lyases; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D011549:Pseudomonas / Q000201:enzymology; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014961:X-Ray Diffraction
chemical_list: D007535:Isomerases; D019998:Racemases and Epimerases; C021540:mandelate racemase; D019753:Intramolecular Lyases; C021811:muconate cycloisomerase