title: Structure-function relationship in an archaebacterial methionine sulphoxide reductase B.
abstract: Oxidation of methionine to methionine sulphoxide (MetSO) may lead to loss of molecular integrity and function. This oxidation can be 'repaired' by methionine sulphoxide reductases (MSRs), which reduce MetSO back to methionine. Two structurally unrelated classes of MSRs, MSRA and MSRB, show stereoselectivity towards the S and the R enantiomer of the sulphoxide respectively. Interestingly, these enzymes were even maintained throughout evolution in anaerobic organisms. Here, the activity and the nuclear magnetic resonance (NMR) structure of MTH711, a zinc containing MSRB from the thermophilic, methanogenic archaebacterium Methanothermobacter thermoautotrophicus, are described. The structure appears more rigid as compared with similar MSRBs from aerobic and mesophilic organisms. No significant structural differences between the oxidized and the reduced MTH711 state can be deduced from our NMR data. A stable sulphenic acid is formed at the catalytic Cys residue upon oxidation of the enzyme with MetSO. The two non-zinc-binding cysteines outside the catalytic centre are not necessary for activity of MTH711 and are not situated close enough to the active-site cysteine to serve in regenerating the active centre via the formation of an intramolecular disulphide bond. These findings imply a reaction cycle that differs from that observed for other MSRBs.
authors.affiliation: Leibniz-Institut für Altersforschung Fritz-Lipmann-Institut, Beutenbergstr. 11, D-07745 Jena, Germany.
authors.forename: Michela
authors.initials: M
authors.lastname: Carella
authors.forename: Juliane
authors.initials: J
authors.lastname: Becher
authors.forename: Oliver
authors.initials: O
authors.lastname: Ohlenschläger
authors.forename: Ramadurai
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Gührs
authors.forename: Gerd
authors.initials: G
authors.lastname: Wellenreuther
authors.forename: Wolfram
authors.initials: W
authors.lastname: Meyer-Klaucke
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Matthias
authors.initials: M
authors.lastname: Görlach
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D017013:Methanobacteriaceae / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D019843:Archaeal Proteins; D008715:Methionine; D051150:Methionine Sulfoxide Reductases