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PDBsum entry 3cpa

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protein ligands metals links
Hydrolase (c-terminal peptidase) PDB id
3cpa
Jmol
Contents
Protein chain
307 a.a. *
Ligands
GLY-TYR
Metals
_ZN
* Residue conservation analysis
PDB id:
3cpa
Name: Hydrolase (c-terminal peptidase)
Title: X-ray crystallographic investigation of substrate binding to carboxypeptidase a at subzero temperature
Structure: Carboxypeptidase a. Chain: a. Engineered: yes
Source: Bos taurus. Bovine. Organism_taxid: 9913. Tissue: pancreas
Resolution:
2.00Å     R-factor:   not given    
Authors: W.N.Lipscomb
Key ref: D.W.Christianson and W.N.Lipscomb (1986). X-ray crystallographic investigation of substrate binding to carboxypeptidase A at subzero temperature. Proc Natl Acad Sci U S A, 83, 7568-7572. PubMed id: 3463986 DOI: 10.1073/pnas.83.20.7568
Date:
24-Mar-82     Release date:   29-Jul-82    
Supersedes: 1cpa
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 9 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 = GLY)
matches with 66.00% 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: 10.1073/pnas.83.20.7568 Proc Natl Acad Sci U S A 83:7568-7572 (1986)
PubMed id: 3463986  
 
 
X-ray crystallographic investigation of substrate binding to carboxypeptidase A at subzero temperature.
D.W.Christianson, W.N.Lipscomb.
 
  ABSTRACT  
 
A high-resolution x-ray crystallographic investigation of the complex between carboxypeptidase A (CPA; peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and the slowly hydrolyzed substrate glycyl-L-tyrosine was done at -9 degrees C. Although this enzyme-substrate complex has been the subject of earlier crystallographic investigation, a higher resolution electron-density map of the complex with greater occupancy of the substrate was desired. All crystal chemistry (i.e., crystal soaking and x-ray data collection) was performed on a diffractometer-mounted flow cell, in which the crystal was immobilized. The x-ray data to 1.6-A resolution have yielded a well-resolved structure in which the zinc ion of the active site is five-coordinate: three enzyme residues (glutamate-72, histidine-69, and histidine-196) and the carbonyl oxygen and amino terminus of glycyl-L-tyrosine complete the coordination polyhedron of the metal. These results confirm that this substrate may be bound in a nonproductive manner, because the hydrolytically important zinc-bound water has been displaced and excluded from the active site. It is likely that all dipeptide substrates of carboxypeptidase A that carry an unprotected amino terminus are poor substrates because of such favorable bidentate coordination to the metal ion of the active site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19480013 A.V.Kilshtain, and A.Warshel (2009).
On the origin of the catalytic power of carboxypeptidase A and other metalloenzymes.
  Proteins, 77, 536-550.  
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.  
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
17391648 J.R.Hershfield, N.Pattabiraman, C.N.Madhavarao, and M.A.Namboodiri (2007).
Mutational analysis of aspartoacylase: implications for Canavan disease.
  Brain Res, 1148, 1.  
17651235 S.Prabhakar, M.S.Chen, E.N.Elpidina, K.S.Vinokurov, C.M.Smith, J.Marshall, and B.Oppert (2007).
Sequence analysis and molecular characterization of larval midgut cDNA transcripts encoding peptidases from the yellow mealworm, Tenebrio molitor L.
  Insect Mol Biol, 16, 455-468.  
16122691 D.Vollhardt (2005).
Effect of interfacial molecular recognition of non-surface-active species on the main characteristics of monolayers.
  Adv Colloid Interface Sci, 116, 63-80.  
12395431 V.Kairys, and M.K.Gilson (2002).
Enhanced docking with the mining minima optimizer: acceleration and side-chain flexibility.
  J Comput Chem, 23, 1656-1670.  
10955996 D.M.van Aalten, C.R.Chong, and L.Joshua-Tor (2000).
Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes.
  Biochemistry, 39, 10082-10089.
PDB code: 1f57
10092856 S.Darnis, N.Juge, C.Marino, F.X.Avilés, A.Puigserver, J.C.Chaix, and X.J.Guo (1999).
Cloning, sequencing and functional expression of a cDNA encoding porcine pancreatic preprocarboxypeptidase A1.
  Eur J Biochem, 259, 719-725.  
9867434 H.M.Greenblatt, H.Feinberg, P.A.Tucker, and G.Shoham (1998).
Carboxypeptidase A: native, zinc-removed and mercury-replaced forms.
  Acta Crystallogr D Biol Crystallogr, 54, 289-305.
PDB codes: 1arl 1arm 1yme
9211842 A.D.Mesecar, B.L.Stoddard, and D.E.Koshland (1997).
Orbital steering in the catalytic power of enzymes: small structural changes with large catalytic consequences.
  Science, 277, 202-206.
PDB codes: 1ai2 1ai3
8894106 S.S.Ghosh, S.Dakoji, Y.Tanaka, Y.J.Cho, and S.Mobashery (1996).
Properties of analogues of an intermediate in the process of mechanism-based inactivation of carboxypeptidase A.
  Bioorg Med Chem, 4, 1487-1492.  
8590009 B.L.Stoddard, and G.K.Farber (1995).
Direct measurement of reactivity in the protein crystal by steady-state kinetic studies.
  Structure, 3, 991-996.  
7592564 E.K.Jaffe (1995).
Porphobilinogen synthase, the first source of heme's asymmetry.
  J Bioenerg Biomembr, 27, 169-179.  
7876902 G.Klebe, and T.Mietzner (1994).
A fast and efficient method to generate biologically relevant conformations.
  J Comput Aided Mol Des, 8, 583-606.  
  1304880 D.C.Richardson, and J.S.Richardson (1992).
The kinemage: a tool for scientific communication.
  Protein Sci, 1, 3-9.  
  1304887 E.Meyer (1992).
Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications.
  Protein Sci, 1, 1543-1562.  
1576995 H.Nar, R.Huber, A.Messerschmidt, A.C.Filippou, M.Barth, M.Jaquinod, M.van de Kamp, and G.W.Canters (1992).
Characterization and crystal structure of zinc azurin, a by-product of heterologous expression in Escherichia coli of Pseudomonas aeruginosa copper azurin.
  Eur J Biochem, 205, 1123-1129.
PDB code: 1e67
1730223 S.Mangani, P.Carloni, and P.Orioli (1992).
X-ray diffraction study of the interaction between carboxypeptidase A and (S)-(+)-1-amino-2-phenylethyl phosphonic acid.
  Eur J Biochem, 203, 173-177.  
1935964 M.Sterk, and H.Gehring (1991).
Spectroscopic characterization of true enzyme-substrate intermediates of aspartate aminotransferase trapped at subzero temperatures.
  Eur J Biochem, 201, 703-707.  
2300547 S.Mobashery, S.S.Ghosh, S.Y.Tamura, and E.T.Kaiser (1990).
Design of an effective mechanism-based inactivator for a zinc protease.
  Proc Natl Acad Sci U S A, 87, 578-582.  
  2691213 M.J.Kronman (1989).
Metal-ion binding and the molecular conformational properties of alpha lactalbumin.
  Crit Rev Biochem Mol Biol, 24, 565-667.  
3422451 G.Shoham, D.W.Christianson, and D.A.Oren (1988).
Complex between carboxypeptidase A and a hydrated ketomethylene substrate analogue.
  Proc Natl Acad Sci U S A, 85, 684-688.  
3470737 D.W.Christianson, P.R.David, and W.N.Lipscomb (1987).
Mechanism of carboxypeptidase A: hydration of a ketonic substrate analogue.
  Proc Natl Acad Sci U S A, 84, 1512-1515.  
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.