Double-duty isomerases: a case study of isomerization-coupled enzymatic catalysis.

The biosynthesis of 11- cis -retinoids by the isomerohydrolase RPE65 and isomero-oxygenase NinaB has recently been described in molecular detail, revealing an unexpected functional convergence of their isomerase activities. Recent structure–function studies have elucidated the mechanisms of other enzymatically catalyzed reactions that involve isomerization coupled with a second reaction type occurring within a single active site. Through comparative enzymology analysis, we find that enzymes catalyzing these in situ coupled reactions participate in diverse biochemical pathways but are often involved in terpenoid metabolism and frequently catalyze alkene bond transformations such as cis–trans isomerization or allylic rearrangements. Active-site steric factors are often pivotal in driving the isomerization reaction. We draw attention to issues surrounding classification and nomenclature of multi-acting enzymes. 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. [ABSTRACT FROM AUTHOR]