Accuracy-rate tradeoffs: how do enzymes meet demands of selectivity and catalytic efficiency?

摘要

I discuss some physico-chemical and evolutionary aspects of enzyme accuracy (selectivity, specificity) and speed (turnover rate, processivity). Accuracy can be a beneficial side-product of active-sites being refined to proficiently convert a given substrate into one product. However, exclusion of undesirable, non-cognate substrates is also an explicitly evolved trait that may come with a cost. I define two schematic mechanisms. Ground-state discrimination applies to enzymes where selectivity is achieved primarily at the level of substrate binding. Exemplified by DNA methyltransferases and the ribosome, ground-state discrimination imposes strong accuracy-rate tradeoffs. Alternatively, transition-state discrimination, applies to relatively small substrates where substrate binding and chemistry are efficiently coupled, and evokes weaker tradeoffs. Overall, the mechanistic, structural and evolutionary basis of enzymatic accuracy-rate tradeoffs merits deeper understanding.