Enzymes can usually be unambiguously assigned to one of seven classes specifying the basic chemistry of their catalyzed reactions. Less frequently, two or more reaction classes are catalyzed by a single enzyme within one active site. Two examples are an isomerohydrolase and an isomero-oxygenase that catalyze isomerization-coupled reactions crucial for production of vision-supporting 11-cis-retinoids. In these enzymes, isomerization is obligately paired and mechanistically intertwined with a second reaction class. A handful of other enzymes carrying out similarly coupled isomerization reactions have been described, some of which have been subjected to detailed structure-function analyses. Herein we review these rarefied enzymes, focusing on the mechanistic and structural basis of their reaction coupling with the goal of revealing catalytic commonalities.

A homologous pair of stereospecific NAD-dependent enzymes, (R)- and (S)-hydroxypropyl-coenzyme M dehydrogenase, are part of a bacterial pathway of short-chain alkene and epoxide metabolism. Their discovery and study, which spans multiple publications over more than a decade, is a data rich story that combines both classical and contemporary experimental biochemistry. A subset of the data for characterization of the recombinant enzymes was used as a case study to augment the teaching of enzyme kinetics and stereoselectivity in an undergraduate biochemistry course at California State University-Chico. © 2018 International Union of Biochemistry and Molecular Biology, 47(2): 124-132, 2019.