Restructuring catalysis in the mandelate pathway.
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.
Neidhart
D C
DC
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
Howell
P L
PL
Petsko
G A
GA
Gerlt
J A
JA
Kozarich
J W
JW
Powers
V M
VM
Kenyon
G L
GL
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
D008333:Mandelic Acids; D007535:Isomerases; D019998:Racemases and Epimerases; C021540:mandelate racemase; D019753:Intramolecular Lyases; C021811:muconate cycloisomerase; C037938:mandelic acid