Conserved patterns in the Cu,Zn superoxide dismutase family.

Abstract:

:Conserved structural and functional features of Cu,Zn superoxide dismutase enzymes have been studied by comparison of known three-dimensional structures and analysis of the currently available amino acid sequences. For this purpose, the three-dimensional structures of the bovine, spinach and yeast enzymes have been superimposed and the structure-based sequence alignment of 38 different superoxide dismutases has been produced. The evolutionary tree obtained from the alignment indicates that cytosolic and extracellular enzymes followed independent evolutionary paths, and that horizontal gene transfer, if any, occurred at an early stage in eukaryota evolution. Based on the sequence alignment and on the analysis of clusters of spatially neighboring residues, the conservation/variation of functionally relevant intramolecular interactions has been investigated. Seven alternative residue arrangements have been identified in the upper rim of the active site, which form an important determinant of the electrostatic field at the catalytic center. The total nominal charge of this region is constantly -1 through the phyla. The seven residues which coordinate the two metal ions at the active site are conserved, with only one known exception. Among the residues involved in maintenance of the active site structure, Gly59, Gly80, Gly136 and Gly139 are fully conserved; mutations of Gly42 and Pro64 have been observed, concerted with replacements in their structural surroundings. Coordinated mutations affecting residue pairs which maintain the packing geometry of the Greek-key beta-barrel have been identified. Furthermore, the unique disulfide bridge involving Cys55-Cys144 in eukaryota, shows the alternative Cys50A-Cys144 arrangement in prokaryotic enzymes.

journal_name

J Mol Biol

authors

Bordo D,Djinović K,Bolognesi M

doi

10.1006/jmbi.1994.1298

subject

Has Abstract

pub_date

1994-05-06 00:00:00

pages

366-86

issue

3

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(84)71298-8

journal_volume

238

pub_type

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