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PDBsum entry 1f57

Go to PDB code: 
protein ligands metals links
Hydrolase PDB id
1f57
Jmol
Contents
Protein chain
307 a.a. *
Ligands
DCY
Metals
_ZN
Waters ×261
* Residue conservation analysis
PDB id:
1f57
Name: Hydrolase
Title: Carboxypeptidase a complex with d-cysteine at 1.75 a
Structure: Carboxypeptidase a. Chain: a. Ec: 3.4.17.1
Source: Bos taurus. Cattle. Organism_taxid: 9913
Resolution:
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
Date:
13-Jun-00     Release date:   06-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00730  (CBPA1_BOVIN) -  Carboxypeptidase A1
Seq:
Struc:
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.3.4.17.1  - 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.
 
  ABSTRACT  
 
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.  
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 codes are shown on the right.