Transition structures in vacuo and the theory of enzyme catalysis. Rubisco's catalytic mechanism: a paradigmatic case?

Abstract

The molecular mechanism of Rubisco is discussed from the theoretical perspective provided by saddle points of index 1 (SPi-1) for the enolization, carboxylation and oxygenation of Rubisco's substrate, d-ribulose-1,5-bisphosphate, by using 3,4-dihydroxy-2-pentanone as substrate model and ab initio SCF MO at a 3-21G basis set level of theory. Intramolecular hydrogen transfer is shown to be a possible pathway for enolization. The geometric conformation of the in vacuo carboxylation transition structure is found to be superimposable on the transition state analogue bound to Rubisco. For oxygenation, the lowest energy SPi-1 has a triplet spin electronic structure and the carbon fragment has a large structural overlap with the C-fragment of the enolization and carboxylation SPi-1 structures. An explanation for the bifunctionality of the Rubisco enzyme arises from these structural similarities: once the catalytic process begins and the transition structure for the enolization step is reached, the system can catalyse both the carboxylation and the oxygenation processes with very little structural changes of the substrate moiety. Thus, depending on the gas molecule that enters into the active site, CO2 or O2, Rubisco will catalyse carboxilation or oxygenation of the substrate, respectively. The “inevitability” hypothesis for the oxygenation reaction is given theoretical support.