J. Phys. Chem. B, 108 (41), 16250 -16254, 2004. 10.1021/jp048788l S1089-5647(04)08788-7

Theoretical Modeling of Enzyme Reaction Chemistry: The Electron Transfer of the Reduction Mechanism in CuZn Superoxide Dismutase

Maira D'Alessandro, Massimiliano Aschi,* Maurizio Paci, Alfredo Di Nola, and Andrea Amadei*

Dipartimento di Scienze e Tecnologie Chimiche, Universita` di Roma "Tor Vergata", via della Ricerca Scientifica 1, 00133 Roma, Italy, Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universita` degli studi dell'Aquila, via Vetoio, 67010 L'Aquila, Italy, and Dipartimento di Chimica, Universita` di Roma "La Sapienza", P. le Aldo Moro 5, 00185 Roma, Italy

Received: March 18, 2004

In Final Form: June 21, 2004

FULL TEXT

Abstract

In this paper, we investigate the first step of the copper-zinc superoxide dismutase enzymatic cycle, involving the binding of a superoxide anion, the transfer of one electron toward the copper, and the simultaneous detachment of His63. By means of combining the perturbed matrix method (PMM) [Chem. Phys. Lett. 2001, 365, 450-456] with basic statistical mechanical relations, presented in the accompanying paper, we describe the coupling between these chemical events and the atomic motions of the complex environment of the reaction center. Results clearly show that the protein-solvent environment fluctuations are essential to understand the reaction mechanism which is based on the concerted rupture of the copper-histidine coordination bond and the copper-superoxide bond in the active site.