title: Solution structure of a functional biomimetic and mechanistic implications for nickel superoxide dismutases.
abstract: The nickel complex of a synthetic nonapeptide (HCDLPCFVY-NH2) is capable of catalytically disproportionating O2(.-) and is thus a functional biomimetic for nickel superoxide dismutases. This represents a simplification as compared to a NiSOD "maquette" that is based on a dodecapeptide that was recently reported [Inorg. Chem. 2006, 45, 2358]. The 3D solution structure reveals that the first six residues form a stable macrocyclic structure with a preformed binding site for Ni(II). Proline 5 exhibits a trans peptide linkage in the biomimetic and a cis conformation in NiSOD enzymes. DFT calculations reveal the source of this preference. Mechanistic consequences for the mode of action (identity of the fifth ligand) are discussed. The SOD activity is compared to enzymatic systems, and selected modifications allowed the biomimetic to be reduced to a functional minimal motif of only six amino acids (ACAAPC-NH2).
authors.affiliation: Leibniz-Institut für Altersforschung, Beutenbergstrasse 11, 07745 Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahn
authors.forename: Michela
authors.initials: M
authors.lastname: Carella
authors.forename: Oliver
authors.initials: O
authors.lastname: Ohlenschläger
authors.forename: Matthias
authors.initials: M
authors.lastname: Görlach
authors.forename: Erika
authors.initials: E
authors.lastname: Kothe
authors.forename: James
authors.initials: J
authors.lastname: Weston
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism*; D009532:Nickel / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D011789:Quantum Theory; D012996:Solutions; D013302:Streptomyces / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D012996:Solutions; D009532:Nickel; D011392:Proline; D013482:Superoxide Dismutase