Despite slow catalysis and confused substrate specificity, all ribulose bisphosphate carboxylases may be nearly perfectly optimized

The cornerstone of autotrophy, the CO(2)-fixing enzyme, d-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), is hamstrung by slow catalysis and confusion between CO(2) and O(2) as substrates, an "abominably perplexing" puzzle, in Darwin's parlance. Here we argue that these characteristics stem from difficulty in binding the featureless CO(2) molecule, which forces specificity for the gaseous substrate to be determined largely or completely in the transition state. We hypothesize that natural selection for greater CO(2)/O(2) specificity, in response to reducing atmospheric CO(2):O(2) ratios, has resulted in a transition state for CO(2) addition in which the CO(2) moiety closely resembles a carboxylate…