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Mutational analysis of divalent metal ion binding in the active site of class II α-mannosidase from Sulfolobus solfataricus.
Hansen, Dennis K; Webb, Helen; Nielsen, Jonas Willum; Harris, Pernille; Winther, Jakob R; Willemoës, Martin.
Afiliación
  • Hansen DK; †Section for Biomolecular Sciences, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
  • Webb H; †Section for Biomolecular Sciences, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
  • Nielsen JW; †Section for Biomolecular Sciences, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
  • Harris P; ‡Department of Chemistry, Technical University of Denmark, Building 206, DK2800 Kgs. Lyngby, Denmark.
  • Winther JR; †Section for Biomolecular Sciences, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
  • Willemoës M; †Section for Biomolecular Sciences, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
Biochemistry ; 54(11): 2032-9, 2015 Mar 24.
Article en En | MEDLINE | ID: mdl-25751413
Mutational analysis of Sulfolobus solfataricus class II α-mannosidase was focused on side chains that interact with the hydroxyls of the -1 mannosyl of the substrate (Asp-534) or form ligands to the active site divalent metal ion (His-228 and His-533) judged from crystal structures of homologous enzymes. D534A and D534N appeared to be completely inactive. When compared to the wild-type enzyme, the mutant enzymes in general showed only small changes in K(M) for the substrate, p-nitrophenyl-α-mannoside, but elevated activation constants, K(A), for the divalent metal ion (Co²âº, Zn²âº, Mn²âº, or Cd²âº). Some mutant enzyme forms displayed an altered preference for the metal ion compared to that of the wild type-enzyme. Furthermore, the H228Q, H533E, and H533Q enzymes were inhibited at increasing Zn²âº concentrations. The catalytic rate was reduced for all enzymes compared to that of the wild-type enzyme, although less dramatically with some activating metal ions. No major differences in the pH dependence between wild-type and mutant enzymes were found in the presence of different metal ions. The pH optimum was 5, but enzyme instability was observed at pH <4.5; therefore, only the basic limb of the bell-shaped pH profile was analyzed.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cationes Bivalentes / Proteínas Arqueales / Alfa-Manosidasa / Sulfolobus solfataricus / Proteínas Mutantes / Metales Idioma: En Revista: Biochemistry Año: 2015 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cationes Bivalentes / Proteínas Arqueales / Alfa-Manosidasa / Sulfolobus solfataricus / Proteínas Mutantes / Metales Idioma: En Revista: Biochemistry Año: 2015 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos