PDBsum entry 1f57

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protein ligands metals links
Hydrolase PDB id
Protein chain
307 a.a. *
Waters ×261
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Carboxypeptidase a complex with d-cysteine at 1.75 a
Structure: Carboxypeptidase a. Chain: a. Ec:
Source: Bos taurus. Cattle. Organism_taxid: 9913
1.75Å     R-factor:   0.137     R-free:   0.164
Authors: D.M.Van Aalten,C.R.Chong,L.Joshua-Tor
Key ref:
D.M.van Aalten et al. (2000). Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes. Biochemistry, 39, 10082-10089. PubMed id: 10955996 DOI: 10.1021/bi000952h
13-Jun-00     Release date:   06-Sep-00    
Go to PROCHECK summary

Protein chain
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 2 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


Bound ligand (Het Group name = DCY)
matches with 62.00% similarity
      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: 10.1021/bi000952h Biochemistry 39:10082-10089 (2000)
PubMed id: 10955996  
Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes.
D.M.van Aalten, C.R.Chong, L.Joshua-Tor.
D-Cysteine differs from the antiarthritis drug D-penicillamine by only two methyl groups on the beta-carbon yet inhibits carboxypeptidase A (CPD) by a distinct mechanism: D-cysteine binds tightly to the active site zinc, while D-penicillamine catalyzes metal removal. To investigate the structural basis for this difference, we solved the crystal structure of carboxypeptidase A complexed with D-cysteine (D-Cys) at 1.75-A resolution. D-Cys binds the active site zinc with a sulfur ligand and forms additional interactions with surrounding side chains of the enzyme. The structure explains the difference in potency between D-Cys and L-Cys and provides insight into the mechanism of D-penicillamine inhibition. D-Cys binding induces a concerted motion of the side chains around the zinc ion, similar to that found in other carboxypeptidase-inhibitor crystal structures and along a limited path. Analysis of concerted motions of CPD and CPD-inhibitor crystal structures reveals a clustering of these structures into distinct groups. Using the restricted conformational flexibility of a drug target in this type of analysis could greatly enhance efficiency in drug design.

Literature references that cite this PDB file's key reference

  PubMed id Reference
14962382 D.Komander, G.S.Kular, A.W.Schüttelkopf, M.Deak, K.R.Prakash, J.Bain, M.Elliott, M.Garrido-Franco, A.P.Kozikowski, D.R.Alessi, and D.M.van Aalten (2004).
Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1.
  Structure, 12, 215-226.
PDB codes: 1uu3 1uu7 1uu8 1uu9 1uvr
12639952 J.Vreede, M.A.van der Horst, K.J.Hellingwerf, W.Crielaard, and D.M.van Aalten (2003).
PAS domains. Common structure and common flexibility.
  J Biol Chem, 278, 18434-18439.
PDB code: 1odv
12169624 R.M.Biondi, D.Komander, C.C.Thomas, J.M.Lizcano, M.Deak, D.R.Alessi, and D.M.van Aalten (2002).
High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site.
  EMBO J, 21, 4219-4228.
PDB code: 1h1w
11484222 F.R.Salsbury, M.F.Crowley, and C.L.Brooks (2001).
Modeling of the metallo-beta-lactamase from B. fragilis: structural and dynamic effects of inhibitor binding.
  Proteins, 44, 448-459.  
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