PDBsum entry 1hdu

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Carboxypeptidase PDB id
Protein chains
307 a.a. *
ING ×4
_ZN ×4
Waters ×591
* Residue conservation analysis
PDB id:
Name: Carboxypeptidase
Title: Crystal structure of bovine pancreatic carboxypeptidase a complexed with aminocarbonylphenylalanine at 1.75 a
Structure: Carboxypeptidase a. Chain: a, b, d, e. Ec:
Source: Bos bovis. Bovine. Organism_taxid: 9913. Organ: pancreas
1.75Å     R-factor:   0.198     R-free:   0.229
Authors: J.H.Cho,N.-C.Ha,S.J.Chung,D.H.Kim,K.Y.Choi,B.-H.Oh
Key ref: J.H.Cho et al. (2002). Insight into the stereochemistry in the inhibition of carboxypeptidase A with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an enantiomeric pair of the inhibitor to carboxypeptidase A. Bioorg Med Chem, 10, 2015-2022. PubMed id: 11937361 DOI: 10.1016/S0968-0896(01)00429-1
17-Nov-00     Release date:   15-Nov-01    
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Protein chains
Pfam   ArchSchema ?
P00730  (CBPA1_BOVIN) -  Carboxypeptidase A1
419 a.a.
307 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Carboxypeptidase A.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidyl-L-amino acid + H2O = peptide + L-amino acid

      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     zinc ion binding     2 terms  


    Added reference    
DOI no: 10.1016/S0968-0896(01)00429-1 Bioorg Med Chem 10:2015-2022 (2002)
PubMed id: 11937361  
Insight into the stereochemistry in the inhibition of carboxypeptidase A with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an enantiomeric pair of the inhibitor to carboxypeptidase A.
J.H.Cho, D.H.Kim, S.J.Chung, N.C.Ha, B.H.Oh, K.Yong Choi.
Both D- and L-isomers of N-(hydroxyaminocarbonyl)phenylalanine () were shown to have strong binding affinity towards carboxypeptidase A (CPA) with D- being more potent than its enantiomer by 3-fold (Chung, S. J.; Kim, D. H. Bioorg. Med. Chem. 2001, 9, 185.). In order to understand the reversed stereochemical preference shown in the CPA inhibition, we have solved the crystal structures of CPA complexed with each enantiometer of up to 1.75 A resolution. Inhibitor L- whose stereochemistry belongs to the stereochemical series of substrate binds CPA like substrate does with its carbonyl oxygen coordinating to the active site zinc ion. Its hydroxyl is engaged in hydrogen bonding with the carboxylate of Glu-270. On the other hand, in binding of D- to CPA, its terminal hydroxyl group is involved in interactions with the active site zinc ion and the carboxylate of Glu-270. In both CPA small middle dot complexes, the phenyl ring in is fitted in the substrate recognition pocket at the S(1)' subsite, and the carboxylate of the inhibitors forms bifurcated hydrogen bonds with the guanidinium moiety of Arg-145 and a hydrogen bond with the guanidinium of Arg-127. In the complex of CPA small middle dotD-, the carboxylate of the inhibitor is engaged in hydrogen bonding with the phenolic hydroxyl of the down-positioned Tyr-248. While the L- binding induces a concerted movement of the backbone amino acid residues at the active site, only the downward movement of Tyr-248 was noted when D- binds to CPA.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20229282 D.Haller, P.Ekici, A.Friess, and H.Parlar (2010).
High enrichment of MMP-9 and carboxypeptidase A by tweezing adsorptive bubble separation (TABS).
  Appl Biochem Biotechnol, 162, 1547-1557.  
19552427 D.Xu, and H.Guo (2009).
Quantum mechanical/molecular mechanical and density functional theory studies of a prototypical zinc peptidase (carboxypeptidase A) suggest a general acid-general base mechanism.
  J Am Chem Soc, 131, 9780-9788.  
17334823 K.H.Kim (2007).
Outliers in SAR and QSAR: is unusual binding mode a possible source of outliers?
  J Comput Aided Mol Des, 21, 63-86.  
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