PDBsum entry 1bcr

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Hydrolase/hydrolase inhibitor PDB id
Protein chains
254 a.a. *
152 a.a. *
Waters ×192
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Complex of the wheat serine carboxypeptidase, cpdw-ii, with microbial peptide aldehyde inhibitor, antipain, and arginin temperature
Structure: Serine carboxypeptidase ii. Chain: a. Serine carboxypeptidase ii. Chain: b. Antipain. Chain: c. Engineered: yes
Source: Triticum aestivum. Bread wheat. Organism_taxid: 4565. Tissue: wheat germ. Synthetic: yes. Actinobacteria. Organism_taxid: 1760
2.50Å     R-factor:   0.162    
Authors: T.L.Bullock,S.J.Remington
Key ref:
T.L.Bullock et al. (1996). Peptide aldehyde complexes with wheat serine carboxypeptidase II: implications for the catalytic mechanism and substrate specificity. J Mol Biol, 255, 714-725. PubMed id: 8636973 DOI: 10.1006/jmbi.1996.0058
03-Nov-95     Release date:   08-Mar-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08819  (CBP2_WHEAT) -  Serine carboxypeptidase 2
444 a.a.
254 a.a.
Protein chain
Pfam   ArchSchema ?
P08819  (CBP2_WHEAT) -  Serine carboxypeptidase 2
444 a.a.
152 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Carboxypeptidase D.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential release of a C-terminal arginine or lysine residue.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     serine-type carboxypeptidase activity     1 term  


DOI no: 10.1006/jmbi.1996.0058 J Mol Biol 255:714-725 (1996)
PubMed id: 8636973  
Peptide aldehyde complexes with wheat serine carboxypeptidase II: implications for the catalytic mechanism and substrate specificity.
T.L.Bullock, K.Breddam, S.J.Remington.
The structures of two ternary complexes of wheat serine carboxypeptidase II (CPD-WII), with a tetrapeptide aldehyde and a reaction product arginine, have been determined by X-ray crystallography at room temperature and -170 degrees. The peptide aldehydes, antipain and chymostatin, form covalent adducts with the active-site serine 146. The CPD-WII antipain arginine model has a standard crystallographic R-factor of 0.162, with good geometry at 2.5 A resolution for data collected at room temperature. The -170 degrees C model of the chymostatin arginine complex has an R-factor of 0.174, with good geometry using data to 2.1 A resolution. The structures suggest binding subsites N-terminal to the scissile bond. All four residues of chymostatin are well-localized in the putative S1 through S4 sites, while density is apparent only in S1 and S2 for antipain. In the S1 site, Val340 and 341, Phe215 and Leu216 form a hydrophobic binding surface, not a pocket, for the P1 phenylalanyl side-chain of chymostatin. The P1 arginyl of antipain also binds at this site, but the positive charge appears to be stabilized by additional solvent molecules. Thus, the hybrid nature of the S1 site accounts for the ability of CPD-WII to accept both hydrophobic and basic residues at P1. Hydrogen bonds to the peptide substrate backbone are few and are made primarily with side-chains on the enzyme. Thus, substrate recognition by CPD-WII appears to have nothing in common with that of the other families of serine proteinases. The hemiacetal linkages to the essential Ser146 are of a single stereoisomer with tetrahedral geometry, with an oxygen atom occupying the "oxyanion hole" region of the enzyme. This atom accepts three hydrogen bonds, two from the polypeptide backbone and one from the positively-charged amino group of bound arginine, and must be negatively charged. Thus, the combination of ligands forms an excellent approximation to the oxyanion intermediate formed during peptide hydrolysis. Surprisingly, the (R) stereochemistry at the hemiacetal linkage is opposite to that expected by comparison to previously determined structures of peptide aldehydes complexed with Streptomyces griseus proteinase A. This is shown to be a consequence of the approximate mirror symmetry of the arrangement of catalytic groups in the two families of serine proteases and suggests that the stereochemical course of the two enzymatic reactions differ in handedness.
  Selected figure(s)  
Figure 1.
Figure 1. The chemical structures of the peptide aldehydes, antipain and chymostatin from Streptomyces. Chymostatin is isolated as a mixture of three forms, A, B, and C. These have R groups of leucine (A), valine (B), or isoleucine (C) side-chains.
Figure 5.
Figure 5. (a) Stereo view of the hydrogen bonding pattern for chy- mostatin (filled bonds) from the refined -170° model. The hydrogen bonds are shown as fine lines and have the indicated lengths in Å . The adjoining residues (open bonds) of CPD-WII form one wall of the active site cavity. (b) Schematic diagram of the hydrogen bond and van der Waals' interactions of the chymo- statin/CPD-WII complex. The bold curves indicate van der Waals' contacts with side-chains of the residues indicated, while broken (b) lines indicate hydrogen bonds.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 255, 714-725) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20460731 H.Morita, K.Kuriyama, N.Akiyama, A.Okamoto, Y.Yamagata, K.Kusumoto, Y.Koide, H.Ishida, and M.Takeuchi (2010).
Molecular cloning of ocpO encoding carboxypeptidase O of Aspergillus oryzae IAM2640.
  Biosci Biotechnol Biochem, 74, 1000-1006.  
17429823 B.M.McArdle, and R.J.Quinn (2007).
Identification of protein fold topology shared between different folds inhibited by natural products.
  Chembiochem, 8, 788-798.  
17145787 G.Birkus, R.Wang, X.Liu, N.Kutty, H.MacArthur, T.Cihlar, C.Gibbs, S.Swaminathan, W.Lee, and M.McDermott (2007).
Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131.
  Antimicrob Agents Chemother, 51, 543-550.  
15809843 Y.Feng, and Q.Xue (2006).
The serine carboxypeptidase like gene family of rice (Oryza sativa L. ssp. japonica).
  Funct Integr Genomics, 6, 14-24.  
16001455 J.C.Kappel, and G.Barany (2005).
Backbone amide linker (BAL) strategy for Nalpha-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of peptide aldehydes.
  J Pept Sci, 11, 525-535.  
15136583 M.Paetzel, J.J.Goodall, M.Kania, R.E.Dalbey, and M.G.Page (2004).
Crystallographic and biophysical analysis of a bacterial signal peptidase in complex with a lipopeptide-based inhibitor.
  J Biol Chem, 279, 30781-30790.
PDB code: 1t7d
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
11741964 M.Paetzel, R.E.Dalbey, and N.C.Strynadka (2002).
Crystal structure of a bacterial signal peptidase apoenzyme: implications for signal peptide binding and the Ser-Lys dyad mechanism.
  J Biol Chem, 277, 9512-9519.
PDB code: 1kn9
11938352 W.T.Lowther, H.Weissbach, F.Etienne, N.Brot, and B.W.Matthews (2002).
The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB.
  Nat Struct Biol, 9, 348-352.
PDB code: 1l1d
11791720 H.Nakase, S.Murata, H.Ueno, and R.Hayashi (2001).
Substrate recognition mechanism of carboxypeptidase Y.
  Biosci Biotechnol Biochem, 65, 2465-2471.  
10713513 M.Fujinaga, M.M.Cherney, N.I.Tarasova, P.A.Bartlett, J.E.Hanson, and M.N.James (2000).
Structural study of the complex between human pepsin and a phosphorus-containing peptidic -transition-state analog.
  Acta Crystallogr D Biol Crystallogr, 56, 272-279.
PDB code: 1qrp
10404588 P.Heikinheimo, A.Goldman, C.Jeffries, and D.L.Ollis (1999).
Of barn owls and bankers: a lush variety of alpha/beta hydrolases.
  Structure, 7, R141-R146.  
9220988 B.H.Shilton, D.Y.Thomas, and M.Cygler (1997).
Crystal structure of Kex1deltap, a prohormone-processing carboxypeptidase from Saccharomyces cerevisiae,.
  Biochemistry, 36, 9002-9012.
PDB code: 1ac5
9432007 F.Goossens, G.Vanhoof, I.De Meester, K.Augustyns, M.Borloo, D.Tourwe, A.Haemers, and S.Scharpé (1997).
Development and evaluation of peptide-based prolyl oligopeptidase inhibitors--introduction of N-benzyloxycarbonyl-prolyl-3-fluoropyrrolidine as a lead in inhibitor design.
  Eur J Biochem, 250, 177-183.  
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.