spacer
spacer

PDBsum entry 2p8o

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Hydrolase PDB id
2p8o
Jmol
Contents
Protein chains
131 a.a. *
95 a.a. *
Ligands
CYS-GLY-VAL-PRO-
ALA-ILE-GLN-PRO-
VAL-LEU
SO4
BVA
Waters ×207
* Residue conservation analysis
PDB id:
2p8o
Name: Hydrolase
Title: Crystal structure of a benzohydroxamic acid/vanadate complex bound to chymotrypsin a
Structure: Chymotrypsin a chain a. Chain: a. Chymotrypsin a chain b. Chain: b. Chymotrypsin a chain c. Chain: c. Ec: 3.4.21.1
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organism_taxid: 9913
Resolution:
1.50Å     R-factor:   0.197     R-free:   0.243
Authors: A.Moulin,J.H.Bell,R.F.Pratt,D.Ringe
Key ref: A.Moulin et al. (2007). Inhibition of chymotrypsin by a complex of ortho-vanadate and benzohydroxamic acid: structure of the inert complex and its mechanistic interpretation. Biochemistry, 46, 5982-5990. PubMed id: 17469803 DOI: 10.1021/bi6025209
Date:
22-Mar-07     Release date:   08-May-07    
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/bi6025209 Biochemistry 46:5982-5990 (2007)
PubMed id: 17469803  
 
 
Inhibition of chymotrypsin by a complex of ortho-vanadate and benzohydroxamic acid: structure of the inert complex and its mechanistic interpretation.
A.Moulin, J.H.Bell, R.F.Pratt, D.Ringe.
 
  ABSTRACT  
 
Serine proteases, like serine beta-lactamases, are rapidly and covalently inhibited by suitably designed phosph(on)ates. The active sites of these enzymes must, therefore, be able to stabilize the pentacoordinated transition states of phosphyl transfer reactions as well as the tetrahedral transition states of acyl transfers. It follows that these enzymes should also be inhibited by molecules capable of generating inert pentacoordinated species. We (J.H.B. and R.F.P.) have previously shown that these enzymes are, in fact, rapidly and reversibly inhibited by 1:1 complexes of vanadate and hydroxamic acids. In this paper, we present the first crystal structure of an acyl transferase inhibited by vanadate. The complex of vanadate and benzohydroxamic acid is a competitive inhibitor of alpha-chymotrypsin with a KI value of 16 muM. In the structure, obtained at a resolution of 1.5 A, the protein is conformationally little different from the apoenzyme. The vanadium, in a distorted octahedral ligand field, is covalently bound to the active site serine oxygen group. One oxgen ligand, presumably anionic, is located in the oxyanion hole. Another is directed roughly in the direction of the acyl transfer leaving group, and a third in the direction of the S2 site. The hydroxamate is bound to vanadium through the hydroxyl oxygen and also, more weakly, through the carbonyl group, to form a five-membered chelate ring. The effect of this chelation is to place the phenyl group of the inhibitor into the important S1 specificity site. The hydroxamate oxygen is directed in line away from the Ser195 Ogamma, approximating the direction of departure of a leaving group in phosphyl transfer. The entire complex can be seen as a reasonable mimic of a phosphyl transfer transition state where the leaving group is extended into the S1 site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19255494 W.R.Novak, A.G.Moulin, M.P.Blakeley, I.Schlichting, G.A.Petsko, and D.Ringe (2009).
A preliminary neutron diffraction study of gamma-chymotrypsin.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 317-320.  
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.