PDBsum entry 2pcu

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Hydrolase PDB id
Protein chain
305 a.a. *
Waters ×270
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Human carboxypeptidase a4 in complex with a cleaved hexapept
Structure: Carboxypeptidase a4. Chain: a. Fragment: carboxypeptidase a4. Synonym: carboxypeptidase a3. Engineered: yes. Peptide. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cpa4, cpa3. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Synthetic: yes. Other_details: chemically synthesised
1.60Å     R-factor:   0.159     R-free:   0.176
Authors: A.Bayes,D.Fernandez,M.Sola,A.Marrero,S.Garcia-Pique,F.X.Avil J.Vendrell,F.X.Gomis-Ruth
Key ref: A.Bayés et al. (2007). Caught after the Act: a human A-type metallocarboxypeptidase in a product complex with a cleaved hexapeptide. Biochemistry, 46, 6921-6930. PubMed id: 17506531 DOI: 10.1021/bi700480b
30-Mar-07     Release date:   17-Apr-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9UI42  (CBPA4_HUMAN) -  Carboxypeptidase A4
421 a.a.
305 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     zinc ion binding     2 terms  


DOI no: 10.1021/bi700480b Biochemistry 46:6921-6930 (2007)
PubMed id: 17506531  
Caught after the Act: a human A-type metallocarboxypeptidase in a product complex with a cleaved hexapeptide.
A.Bayés, D.Fernández, M.Solà, A.Marrero, S.García-Piqué, F.X.Avilés, J.Vendrell, F.X.Gomis-Rüth.
A/B-type metallocarboxypeptidases (MCPs) are among the most thoroughly studied proteolytic enzymes, and their catalytic mechanisms have been considered as prototypes even for several unrelated metalloprote(in)ase families. It has long been postulated that the nature of the side chains of at least five substrate residues, i.e., P4-P1', influence Km and kcat and that once the peptide or protein substrate is cleaved, both products remain in the first instance bound to the active-site cleft of the enzyme in a double-product complex. Structural details of binding of substrate to the nonprimed side of the cleft have largely relied on complexes with protein inhibitors and peptidomimetic small-molecule inhibitors that do not span the entire groove. In the former, the presence of N-terminal globular protein domains participating in large-scale interactions with the surface of the cognate catalytic domain outside the active-site cleft mostly conditions the way their C-terminal tails bind to the cleft. Accordingly, they may not be accurate models for a product complex. We hereby provide the structural details of a true cleaved double-product complex with a hexapeptide of an MCP engaged in prostate cancer, human carboxypeptidase A4, employing diffraction data to 1.6 A resolution (Rcryst and Rfree = 0.159 and 0.176, respectively). These studies provide detailed information about subsites S5-S1' and contribute to our knowledge of the cleavage mechanism, which is revisited in light of these new structural insights.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20526345 P.Van Damme, A.Staes, S.Bronsoms, K.Helsens, N.Colaert, E.Timmerman, F.X.Aviles, J.Vandekerckhove, and K.Gevaert (2010).
Complementary positional proteomics for screening substrates of endo- and exoproteases.
  Nat Methods, 7, 512-515.  
18991561 A.M.Grishin, V.K.h.Akparov, and G.G.Chestukhina (2008).
Leu254 residue and calcium ions as new structural determinants of carboxypeptidase T substrate specificity.
  Biochemistry (Mosc), 73, 1140-1145.  
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