title: Conformational stabilization at the active site of molluskan (Rapana thomasiana) hemocyanin by a cysteine-histidine thioether bridge A study by mass spectrometry and molecular modeling.
abstract: In some type-3 copper proteins (molluskan hemocyanin, catechol oxidase and fungal tyrosinase) one of the histidine residues, liganding the Cu(A) atom of the dinuclear copper active site, is covalently linked to a cysteine residue by a thioether bridge. The purpose of this study was to disclose the function of this bridge. Mass spectral analysis of a peptide, isolated from Rapana thomasiana (gastropodan mollusk) hemocyanin, indicated a stabilization of the peptide structure in the region of the bridge. Molecular modeling of three thioether containing type-3 copper proteins using the dead-end elimination method showed that the concerned histidine would be very flexible if not linked to the cysteine. Also, the side chain orientation of the histidine is rather exceptional, as evidenced by statistical data from the protein databank. It is suggested that the role of the bridge is to fix the histidine in an orientation that is optimal for coordination of the Cu(A) atom.
authors.affiliation: Division of Biochemistry, Molecular and Structural Biology, Chemistry Department, Katholieke Universiteit Leuven, Celestijnenlaan 200 G, 3001 Leuven-Heverlee, Belgium. constant.gielens@chem.kuleuven.be
authors.forename: Constant
authors.initials: C
authors.lastname: Gielens
authors.forename: Krassimira
authors.initials: K
authors.lastname: Idakieva
authors.forename: Marc
authors.initials: M
authors.lastname: De Maeyer
authors.forename: Viviane
authors.initials: V
authors.lastname: Van den Bergh
authors.forename: Nurul Islam
authors.initials: NI
authors.lastname: Siddiqui
authors.forename: Frans
authors.initials: F
authors.lastname: Compernolle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003545:Cysteine / Q000737:chemistry*; D006433:Hemocyanins / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008974:Mollusca / Q000737:chemistry*; D029623:Primulaceae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D006639:Histidine; D006433:Hemocyanins; D003545:Cysteine