Crystal structure of avian carboxypeptidase D domain II

A prototype for the regulatory metallocarboxypeptidase subfamily

F. X. Gomis-Rüth, V. Companys, Y. Qian, Lloyd D. Fricker, J. Vendrell, F. X. Avilés, M. Coll

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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 α/β-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 α/β-hydrolase subdomain is followed by a C-terminal 80 residue β-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.

Original languageEnglish (US)
Pages (from-to)5817-5826
Number of pages10
JournalEMBO Journal
Volume18
Issue number21
DOIs
StatePublished - Nov 1 1999

Fingerprint

Hydrolases
Crystal structure
Carboxypeptidases A
Carboxypeptidases
Tandem Repeat Sequences
Prealbumin
Ducks
Processing
Sugars
Catalytic Domain
Carrier Proteins
Substrates
Enzymes
Proteins
carboxypeptidase D

Keywords

  • Carboxypeptidase
  • Inhibitor design
  • Metalloprotease
  • Transthyretin
  • X-ray crystal structure

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Crystal structure of avian carboxypeptidase D domain II : A prototype for the regulatory metallocarboxypeptidase subfamily. / Gomis-Rüth, F. X.; Companys, V.; Qian, Y.; Fricker, Lloyd D.; Vendrell, J.; Avilés, F. X.; Coll, M.

In: EMBO Journal, Vol. 18, No. 21, 01.11.1999, p. 5817-5826.

Research output: Contribution to journalArticle

Gomis-Rüth, F. X. ; Companys, V. ; Qian, Y. ; Fricker, Lloyd D. ; Vendrell, J. ; Avilés, F. X. ; Coll, M. / Crystal structure of avian carboxypeptidase D domain II : A prototype for the regulatory metallocarboxypeptidase subfamily. In: EMBO Journal. 1999 ; Vol. 18, No. 21. pp. 5817-5826.
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