Crystal structure of avian carboxypeptidase D domain II: a prototype for the regulatory metallocarboxypeptidase subfamily.
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.
Gomis-Rüth
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Institut de Biologia Molecular de Barcelona, CID-CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain.
Companys
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Qian
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Fricker
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Vendrell
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Avilés
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Coll
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004372:Ducks; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010843:Pichia; D017433:Protein Structure, Secondary; D011506:Proteins; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment
D008562:Membrane Glycoproteins; D011506:Proteins; D011994:Recombinant Proteins; D002268:Carboxypeptidases; C094315:metallocarboxypeptidase D