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Mn/Fe superoxide dismutase interaction fingerprints and prediction of oligomerization and metal cofactor from sequence
Author(s) -
Wintjens René,
Gilis Dimitri,
Rooman Marianne
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21650
Subject(s) - subfamily , cofactor , superoxide dismutase , biochemistry , chemistry , sequence (biology) , peptide sequence , mutant , computational biology , enzyme , stereochemistry , biology , gene
Abstract Fe‐ and Mn‐containing superoxide dismutase (sod) enzymes are closely related and similar in both amino acid sequence and structure, but differ in their mode of oligomerization and in their specificity for the Fe or Mn cofactor. The goal of the present work is to identify and analyze the sequence and structure characteristics that ensure the cofactor specificities and the oligomerization modes. For that purpose, 374 sod sequences and 17 sod crystal structures were collected and aligned. These alignments were searched for residues and inter‐residue interactions that are conserved within the whole sod family, or alternatively, that are specific to a given sod subfamily sharing common characteristics. This led us to define key residues and inter‐residue interaction fingerprints in each subfamily. The comparison of these fingerprints allows, on a rational basis, the design of mutants likely to modulate the activity and/or specificity of the target sod, in good agreement with the available experimental results on known mutants. The key residues and interaction fingerprints are furthermore used to predict if a novel sequence corresponds to a sod enzyme, and if so, what type of sod it is. The predictions of this fingerprint method reach much higher scores and present much more discriminative power than the commonly used method that uses pairwise sequence comparisons. Proteins 2008. © 2007 Wiley‐Liss, Inc.