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PDBsum entry 2vgc

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protein ligands Protein-protein interface(s) links
Serine protease PDB id
2vgc
Jmol
Contents
Protein chains
131 a.a. *
95 a.a. *
Ligands
CYS-GLY-VAL-PRO-
ALA-ILE-GLN-PRO-
VAL-LEU
SO4 ×2
V35
Waters ×95
* Residue conservation analysis
PDB id:
2vgc
Name: Serine protease
Title: Gamma-chymotrypsin d-para-chloro-1-acetamido boronic acid inhibitor complex
Structure: Gamma chymotrypsin. Chain: a. Other_details: a-chymotrypsin purchased from sigma and converted to g-chymotrypsin by the method of stoddard et al., 1990, biochemistry, vol. 29, p. 4871-4879. Gamma chymotrypsin. Chain: b. Other_details: a-chymotrypsin purchased from sigma and converted to g-chymotrypsin by the method of stoddard et
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas. Organ: pancreas
Biol. unit: Trimer (from PQS)
Resolution:
1.80Å     R-factor:   0.210     R-free:   0.254
Authors: V.S.Stoll,B.T.Eger,R.C.Hynes,V.Martichonok,J.B.Jones,E.F.Pai
Key ref:
V.S.Stoll et al. (1998). Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes. Biochemistry, 37, 451-462. PubMed id: 9425066 DOI: 10.1021/bi971166o
Date:
01-May-97     Release date:   12-Nov-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00766  (CTRA_BOVIN) -  Chymotrypsinogen A
Seq:
Struc:
245 a.a.
131 a.a.
Protein chain
Pfam   ArchSchema ?
P00766  (CTRA_BOVIN) -  Chymotrypsinogen A
Seq:
Struc:
245 a.a.
95 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains B, C: E.C.3.4.21.1  - Chymotrypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     catalytic activity     2 terms  

 

 
DOI no: 10.1021/bi971166o Biochemistry 37:451-462 (1998)
PubMed id: 9425066  
 
 
Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes.
V.S.Stoll, B.T.Eger, R.C.Hynes, V.Martichonok, J.B.Jones, E.F.Pai.
 
  ABSTRACT  
 
In order to probe the structural basis of stereoselectivity in the serine protease family, a series of enantiomeric boronic acids RCH2CH(NHCOCH3)B(OH)2 has been synthesized and kinetically characterized as transition-state analog inhibitors using alpha-chymotrypsin and subtilisin Carlsberg as model systems. When the R-substituent in this series was changed from a p-chlorophenyl to a 1-naphthyl group, alpha-chymotrypsin, but not subtilisin, reversed its usual preference for l-enantiomers and bound more tightly to the D-enantiomer [Martichonok, V., & Jones, J. B. (1996) J. Am. Chem. Soc. 118, 950-958]. The structural factors responsible for the differences in stereoselectivity between the two enzymes have been explored by X-ray crystallographic examination of subtilisin Carlsberg and gamma-chymotrypsin complexes of the L- and D-enantiomers of p-chlorophenyl and 1-naphthyl boronic acid derivatives. In both enzymes, the L-isomers of the inhibitors, which are more closely related to the natural L-amino acid substrates, form tetrahedral adducts, covalently linking the central boron atom and Ogamma of the catalytic serine. The d-isomers, however, differ in the way they interact with subtilisin or gamma-chymotrypsin. With subtilisin, both the D-p-chlorophenyl and D-1-naphthyl inhibitor complexes form covalent Ser Ogamma-to-boron bonds, but with gamma-chymotrypsin, the same inhibitors lead to novel tetrahedral adducts covalently linking both Ser195 Ogamma and His57 Nepsilon2 covalently via the boron atom.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21280129 D.Lousa, A.M.Baptista, and C.M.Soares (2011).
Structural determinants of ligand imprinting: A molecular dynamics simulation study of subtilisin in aqueous and apolar solvents.
  Protein Sci, 20, 379-386.  
19520822 N.Ghosh, and A.Emadi (2009).
From orbital hybridization to chemotherapeutics neutralization.
  Blood, 113, 6262.  
17849483 D.S.Matteson (2008).
alpha-Amido boronic acids: a synthetic challenge and their properties as serine protease inhibitors.
  Med Res Rev, 28, 233-246.  
15377393 W.Cai, J.Pei, and N.V.Grishin (2004).
Reconstruction of ancestral protein sequences and its applications.
  BMC Evol Biol, 4, 33.  
12481254 M.T.Gallardo-Williams, R.R.Maronpot, R.N.Wine, S.H.Brunssen, and R.E.Chapin (2003).
Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid.
  Prostate, 54, 44-49.  
12416979 C.C.Tseng, S.D.Bruner, R.M.Kohli, M.A.Marahiel, C.T.Walsh, and S.A.Sieber (2002).
Characterization of the surfactin synthetase C-terminal thioesterase domain as a cyclic depsipeptide synthase.
  Biochemistry, 41, 13350-13359.  
11429309 P.Berglund (2001).
Controlling lipase enantioselectivity for organic synthesis.
  Biomol Eng, 18, 13-22.  
11295445 Y.Guo, and D.S.Clark (2001).
Activation of enzymes for nonaqueous biocatalysis by denaturing concentrations of urea.
  Biochim Biophys Acta, 1546, 406-411.  
10328262 T.K.Harris, and A.S.Mildvan (1999).
High-precision measurement of hydrogen bond lengths in proteins by nuclear magnetic resonance methods.
  Proteins, 35, 275-282.  
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.