Single mutation at the intersubunit interface confers extra efficiency to Cu,Zn superoxide dismutase

The Val28 --> Gly single mutant at the subunit interface of Cu,Zn superoxid e dismutase from Photobacterium leiognathi displays a k(cat)/K-M value of 1 .7 x 10(10) M-1 s(-1), twice that of the native enzyme. Analysis of the thr ee-dimensional structure indicates that the active site Cu,Zn center is not perturbed, slight structural deviations being only localized in proximity of the mutation site. The enzyme-substrate association rate, calculated by Brownian dynamics simulation, is identical for both enzymes, indicating tha t the higher catalytic efficiency of the Val28 --> Gly mutant is not due to a more favorable electrostatic potential distribution. This result demonst rates the occurrence of an intramolecular communication between the mutatio n site and the catalytic center, about 18 Angstrom away and indicates a new strategy to encode extra efficiency within other members of this enzymatic family. (C) 2000 Federation of European Biochemical Societies. Published b y Elsevier Science B.V. All rights reserved.