title: Evolutionary conservativeness of electric field in the Cu,Zn superoxide dismutase active site. Evidence for co-ordinated mutation of charged amino acid residues.
abstract: Equipotential lines were calculated, using the Poisson-Boltzmann equation, for six Cu,Zn superoxide dismutases with different protein electric charge and various degrees of sequence homology, namely those from ox, pig, sheep, yeast, and the isoenzymes A and B from the amphibian Xenopus laevis. The three-dimensional structures of the porcine and ovine superoxide dismutases were obtained by molecular modelling reconstruction using the structure of the highly homologous bovine enzyme as a template. The three-dimensional structure of the evolutionary distant yeast Cu,Zn superoxide dismutase was recently resolved by us, while computer-modelled structures are available for X. laevis isoenzymes. The six proteins display large differences in the net protein charge and distribution of electrically charged surface residues but the trend of the equipotential lines in the proximity of the active sites was found to be constant in all cases. These results are in line with the very similar catlytic rate constants experimentally measured for the corresponding enzyme activities. This analysis shows that electrostatic guidance for the enzyme-substrate interaction in Cu,Zn superoxide dismutases is related to a spatial distribution of charges, arranged so as to maintain, in the area surrounding the active sites, an identical electrostatic potential distribution, which is conserved in the evolution of this protein family.
authors.affiliation: Department of Organic and Biological Chemistry, University of Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Desideri
authors.forename: M
authors.initials: M
authors.lastname: Falconi
authors.forename: F
authors.initials: F
authors.lastname: Polticelli
authors.forename: M
authors.initials: M
authors.lastname: Bolognesi
authors.forename: K
authors.initials: K
authors.lastname: Djinovic
authors.forename: G
authors.initials: G
authors.lastname: Rotilio
mesh_terms: D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D002417:Cattle; D004563:Electrochemistry; D005656:Fungal Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012756:Sheep; D013482:Superoxide Dismutase / Q000737:chemistry*; D013552:Swine; D014982:Xenopus laevis
chemical_list: D005656:Fungal Proteins; D013482:Superoxide Dismutase