A minimal kinetic model for the interpretation of complex catalysis in single enzyme molecules.

Abstract

Multi-exponential waiting-time distribution and randomness parameter greater than unity ascribe dynamic disorder in single-enzyme catalysis corroborated to the interplay of transforming conformers [English et al., Nat. Chem. Biol., 2006, 2, 87]. The associated multi-state model of enzymatic turnovers with statically heterogeneous catalytic rates misdescribes the non-linear uprising of the randomness parameter from unity in relation to the attributes of the fall-offs of the waiting-time distribution at different substrate concentrations. To resolve this crucial issue, we first employ a comprehensive stochastic reaction scenario and further rationalize and work out the minimal indispensable dynamic-disorder model that ensures the foregoing relationship upon comparison with the data. We elucidate that specific disregard for the transition rate coefficients in the multi-state model on account of the especially slow conformational transitions is the underlying reason for not achieving interrelation between the observables.