PDBsum entry 1qmu

Go to PDB code: 
protein ligands metals links
Carboxypeptidase PDB id
Protein chain
380 a.a. *
SO4 ×3
Waters ×121
* Residue conservation analysis
PDB id:
Name: Carboxypeptidase
Title: Duck carboxypeptidase d domain ii
Structure: Carboxypeptidase gp180 residues 503-882. Chain: a. Fragment: yes. Engineered: yes
Source: Lophonetta specularioides. Crested duck. Organism_taxid: 8836. Organ: liver. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Other_details: obtained after cloning into and overexpression from a pichia pastoris system.
Biol. unit: Trimer (from PDB file)
2.7Å     R-factor:   0.198     R-free:   0.236
Authors: F.X.Gomis-Rueth,M.Coll,F.X.Aviles,J.Vendrell,L.D.Fricker
Key ref:
F.X.Gomis-Rüth et al. (1999). Crystal structure of avian carboxypeptidase D domain II: a prototype for the regulatory metallocarboxypeptidase subfamily. EMBO J, 18, 5817-5826. PubMed id: 10545093 DOI: 10.1093/emboj/18.21.5817
06-Oct-99     Release date:   13-Oct-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P83852  (CBPD_LOPSP) -  Carboxypeptidase D (Fragment)
380 a.a.
380 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     hydrolase activity     8 terms  


DOI no: 10.1093/emboj/18.21.5817 EMBO J 18:5817-5826 (1999)
PubMed id: 10545093  
Crystal structure of avian carboxypeptidase D domain II: a prototype for the regulatory metallocarboxypeptidase subfamily.
F.X.Gomis-Rüth, V.Companys, Y.Qian, L.D.Fricker, J.Vendrell, F.X.Avilés, M.Coll.
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.
  Selected figure(s)  
Figure 2.
Figure 2 (A) Stereo ribbon cartoon of CPD-2. The termini are labelled, as are the helices (A -I) and strands (I -XV). The zinc ion, the zinc-coordinating protein side chains, the N-linked glycosylation sites, the disulfide bond and the sulfate anions are also displayed. (B) Topology scheme of the CPD-2 polypeptide fold, with -helices indicated by cylinders and -strands by arrows.
Figure 4.
Figure 4 (A) Stereo view of the overlaid C[ ]-carbon structures of CPD-2 (CP subdomain only; yellow sticks), CPA (green sticks) and CPT (magenta sticks). The zinc ion (violet sphere) belongs to the CPD-2 structure. Selected CPD-2 residues are labelled. (B) View facing the funnel surrounding the active site cleft superimposed with its solid Connolly surface displaying the electrostatic potential [ranging from -15 k[B]T/e (red) to +15 k[B]T/e (blue)] of CPD-2 (left), CPA (centre) and CPT (right). The modelled substrate (CPD-2) and the coordinates (PDB access code 6cpa) of a phosphonate inhibitor (CPA and CPT) are also displayed, respectively, to highlight the active site. (C) Stereo view of the C[ ]-carbon structures of CPD-2 (CP subdomain only; yellow sticks) and CPA (green sticks) in its complex with potato carboxypeptidase inhibitor (blue sticks) (PDB access code 4cpa). Steric hindrance prevents the latter from binding the regulatory CP. The zinc ion (violet sphere) belongs to the CPD-2 structure. Some CPD-2 residues are labelled.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 5817-5826) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18566513 I.Pallarès, D.Fernández, M.Comellas-Bigler, J.Fernández-Recio, S.Ventura, F.X.Avilés, W.Bode, and J.Vendrell (2008).
Direct interaction between a human digestive protease and the mucoadhesive poly(acrylic acid).
  Acta Crystallogr D Biol Crystallogr, 64, 784-791.
PDB code: 2v77
18039526 R.A.Skidgel, and E.G.Erdös (2007).
Structure and function of human plasma carboxypeptidase N, the anaphylatoxin inactivator.
  Int Immunopharmacol, 7, 1888-1899.  
17697995 V.Krishnan, A.H.Gaspar, N.Ye, A.Mandlik, H.Ton-That, and S.V.Narayana (2007).
An IgG-like domain in the minor pilin GBS52 of Streptococcus agalactiae mediates lung epithelial cell adhesion.
  Structure, 15, 893-903.
PDB codes: 2pz4 3phs
16556608 G.Sidyelyeva, N.E.Baker, and L.D.Fricker (2006).
Characterization of the molecular basis of the Drosophila mutations in carboxypeptidase D. Effect on enzyme activity and expression.
  J Biol Chem, 281, 13844-13852.  
16384918 J.J.Adams, G.Pal, Z.Jia, and S.P.Smith (2006).
Mechanism of bacterial cell-surface attachment revealed by the structure of cellulosomal type II cohesin-dockerin complex.
  Proc Natl Acad Sci U S A, 103, 305-310.
PDB code: 2b59
16538615 P.J.Lyons, N.R.Mattatall, and H.S.Ro (2006).
Modeling and functional analysis of AEBP1, a transcriptional repressor.
  Proteins, 63, 1069-1083.  
15738388 I.Pallarès, R.Bonet, R.García-Castellanos, S.Ventura, F.X.Avilés, J.Vendrell, and F.X.Gomis-Rüth (2005).
Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin.
  Proc Natl Acad Sci U S A, 102, 3978-3983.
PDB codes: 2bk7 2bo9
12643276 J.B.Walker, B.Hughes, I.James, P.Haddock, C.Kluft, and L.Bajzar (2003).
Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro.
  J Biol Chem, 278, 8913-8921.  
12799375 L.Zhao, B.Buckman, M.Seto, J.Morser, and M.Nagashima (2003).
Mutations in the substrate binding site of thrombin-activatable fibrinolysis inhibitor (TAFI) alter its substrate specificity.
  J Biol Chem, 278, 32359-32366.  
  11836249 S.Wei, S.Segura, J.Vendrell, F.X.Aviles, E.Lanoue, R.Day, Y.Feng, and L.D.Fricker (2002).
Identification and characterization of three members of the human metallocarboxypeptidase gene family.
  J Biol Chem, 277, 14954-14964.  
11976326 Y.Y.Chen, K.J.Cross, R.A.Paolini, J.E.Fielding, N.Slakeski, and E.C.Reynolds (2002).
CPG70 is a novel basic metallocarboxypeptidase with C-terminal polycystic kidney disease domains from Porphyromonas gingivalis.
  J Biol Chem, 277, 23433-23440.  
11602705 H.C.Spangenberg, H.B.Lee, J.Li, F.Tan, R.Skidgel, J.R.Wands, and S.Tong (2001).
A short sequence within domain C of duck carboxypeptidase D is critical for duck hepatitis B virus binding and determines host specificity.
  J Virol, 75, 10630-10642.  
11462236 H.Chen, S.Jawahar, Y.Qian, Q.Duong, G.Chan, A.Parker, J.M.Meyer, K.J.Moore, S.Chayen, D.J.Gross, B.Glaser, M.A.Permutt, and L.D.Fricker (2001).
Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity.
  Hum Mutat, 18, 120-131.  
11438679 M.D.Layne, S.F.Yet, K.Maemura, C.M.Hsieh, M.Bernfield, M.A.Perrella, and M.E.Lee (2001).
Impaired abdominal wall development and deficient wound healing in mice lacking aortic carboxypeptidase-like protein.
  Mol Cell Biol, 21, 5256-5261.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.