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Conserved proline residues prevent dimerization and aggregation in the ß-lactamase BlaC.
Chikunova, A; Manley, M P; Heijjer, C N; Drenth, C S; Cramer-Blok, A J; Ahmad, M Ud Din; Perrakis, A; Ubbink, M.
Afiliación
  • Chikunova A; Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
  • Manley MP; Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
  • Heijjer CN; Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
  • Drenth CS; Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
  • Cramer-Blok AJ; Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
  • Ahmad MUD; Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Perrakis A; Oncode Institute, Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Ubbink M; Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Protein Sci ; 33(4): e4972, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38533527
ABSTRACT
Evolution leads to conservation of amino acid residues in protein families. Conserved proline residues are usually considered to ensure the correct folding and to stabilize the three-dimensional structure. Surprisingly, proline residues that are highly conserved in class A ß-lactamases were found to tolerate various substitutions without large losses in enzyme activity. We investigated the roles of three conserved prolines at positions 107, 226, and 258 in the ß-lactamase BlaC from Mycobacterium tuberculosis and found that mutations can lead to dimerization of the enzyme and an overall less stable protein that is prone to aggregate over time. For the variant Pro107Thr, the crystal structure shows dimer formation resembling domain swapping. It is concluded that the proline substitutions loosen the structure, enhancing multimerization. Even though the enzyme does not lose its properties without the conserved proline residues, the prolines ensure the long-term structural integrity of the enzyme.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prolina / Mycobacterium tuberculosis Idioma: En Revista: Protein Sci Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prolina / Mycobacterium tuberculosis Idioma: En Revista: Protein Sci Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos