title: Specificity and phenetic relationships of iron- and manganese-containing superoxide dismutases on the basis of structure and sequence comparisons.
abstract: The iron- and manganese-containing superoxide dismutases (Fe/Mn-SOD) share the same chemical function and spatial structure but can be distinguished according to their modes of oligomerization and their metal ion specificity. They appear as homodimers or homotetramers and usually require a specific metal for activity. On the basis of 261 aligned SOD sequences and 12 superimposed x-ray structures, two phenetic trees were constructed, one sequence-based and the other structure-based. Their comparison reveals the imperfect correlation of sequence and structural changes; hyperthermophilicity requires the largest sequence alterations, whereas dimer/tetramer and manganese/iron specificities are induced by the most sizable structural differences within the monomers. A systematic investigation of sequence and structure characteristics conserved in all aligned SOD sequences or in subsets sharing common oligomeric and/or metal specificities was performed. Several residues were identified as guaranteeing the common function and dimeric conformation, others as determining the tetramer formation, and yet others as potentially responsible for metal specificity. Some form cation-pi interactions between an aromatic ring and a fully or partially positively charged group, suggesting that these interactions play a significant role in the structure and function of SOD enzymes. Dimer/tetramer- and iron/manganese-specific fingerprints were derived from the set of conserved residues; they can be used to propose selected residue substitutions in view of the experimental validation of our in silico derived hypotheses.
authors.affiliation: Université Libre de Bruxelles, Institut de Pharmacie, Chimie Générale, CP 206/04, Campus de la Plaine, Boulevard du Triomphe, B-1050 Bruxelles, Belgium.
authors.forename: René
authors.initials: R
authors.lastname: Wintjens
authors.forename: Christophe
authors.initials: C
authors.lastname: Noël
authors.forename: Alex C W
authors.initials: AC
authors.lastname: May
authors.forename: Delphine
authors.initials: D
authors.lastname: Gerbod
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dufernez
authors.forename: Monique
authors.initials: M
authors.lastname: Capron
authors.forename: Eric
authors.initials: E
authors.lastname: Viscogliosi
authors.forename: Marianne
authors.initials: M
authors.lastname: Rooman
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D017124:Conserved Sequence; D007501:Iron; D008345:Manganese; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D013482:Superoxide Dismutase / Q000032:analysis / Q000737:chemistry / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008345:Manganese; D007501:Iron; D013482:Superoxide Dismutase