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Crystal structure of avian carboxypeptidase D domain II: a prototype for the regulatory metallocarboxypeptidase subfamily.
Gomis-Rüth, F X; Companys, V; Qian, Y; Fricker, L D; Vendrell, J; Avilés, F X; Coll, M.
Afiliación
  • Gomis-Rüth FX; Institut de Biologia Molecular de Barcelona, CID-CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain.
EMBO J ; 18(21): 5817-26, 1999 Nov 01.
Article en En | MEDLINE | ID: mdl-10545093
The crystal structure of domain II of duck carboxypeptidase D, a prohormone/propeptide processing enzyme integrated in a three repeat tandem in the natural system, has been solved, constituting a prototype for members of the regulatory metallocarboxypeptidase subfamily. It displays a 300 residue N-terminal alpha/beta-hydrolase subdomain with overall topological similarity to and general coincidence of the key catalytic residues with the archetypal pancreatic carboxypeptidase A. However, numerous significant insertions/deletions in segments forming the funnel-like access to the active site explain differences in specificity towards larger protein substrates or inhibitors. This alpha/beta-hydrolase subdomain is followed by a C-terminal 80 residue beta-sandwich subdomain, unique for these regulatory metalloenzymes and topologically related to transthyretin and sugar-binding proteins. The structure described here establishes the fundamentals for a better understanding of the mechanism ruling events such as prohormone processing and will enable modelling of regulatory carboxypeptidases as well as a more rational design of inhibitors of carboxypeptidase D.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Carboxipeptidasas / Proteínas Límite: Animals Idioma: En Revista: EMBO J Año: 1999 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Carboxipeptidasas / Proteínas Límite: Animals Idioma: En Revista: EMBO J Año: 1999 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido