PDBsum entry 2gct

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protein ligands Protein-protein interface(s) links
Hydrolase/peptide PDB id
Protein chains
11 a.a. *
131 a.a. *
95 a.a. *
SO4 ×2
Waters ×131
* Residue conservation analysis
PDB id:
Name: Hydrolase/peptide
Title: Structure of gamma-chymotrypsin in the range ph 2.0 to ph 10 suggests that gamma-chymotrypsin is a covalent acyl-enzyme low ph
Structure: Gamma-chymotrypsin a. Chain: a. Gamma-chymotrypsin a. Chain: b. Gamma-chymotrypsin a. Chain: c. Tetrapeptide adduct. Chain: d. Engineered: yes
Source: Bos taurus. Organism_taxid: 9913.
1.80Å     R-factor:   0.169    
Authors: M.M.Dixon,B.W.Matthews
Key ref: M.M.Dixon et al. (1991). Structure of gamma-chymotrypsin in the range pH 2.0 to pH 10.5 suggests that gamma-chymotrypsin is a covalent acyl-enzyme adduct at low pH. Int J Biol Macromol, 13, 89-96. PubMed id: 1888717 DOI: 10.1016/0141-8130(91)90054-X
04-Sep-90     Release date:   15-Oct-91    
Go to PROCHECK summary

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

 Enzyme reactions 
   Enzyme class: Chains A, B, C: E.C.  - 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: 10.1016/0141-8130(91)90054-X Int J Biol Macromol 13:89-96 (1991)
PubMed id: 1888717  
Structure of gamma-chymotrypsin in the range pH 2.0 to pH 10.5 suggests that gamma-chymotrypsin is a covalent acyl-enzyme adduct at low pH.
M.M.Dixon, R.G.Brennan, B.W.Matthews.
Crystals of gamma-chymotrypsin (gamma-CHT) grown at pH 7.0 are stable from pH 2.0 to 11.0. Crystalline gamma-CHT therefore provides an unusually favourable system to observe the structure of a protein and its bound solvent over a broad range of pH. In this report we describe the high-resolution refined structure of gamma-CHT at pH values of 2.0, 7.0 and 10.5. The apparent tetrapeptide seen bound in the active site of gamma-CHT at pH 7.0 is also present at pH 2.0 and 10.5 although it is better defined at low pH. A comparison of the respective structures shows that there is additional electron density in the low pH structure at the point where the side-chain of Ser 195 approaches most closely to the presumptive inhibitor. This suggests that the adduct is most likely to be covalently linked to the enzyme at low pH and to be non-covalent at higher pH. As the pH is lowered from 7.0 to 2.0, the side-chain of His 40 rotates approximately 120 degrees about its C alpha-C beta bond and, in concert, the side-chain of Gln 34 also rotates approximately 140 degrees about its C alpha-C beta bond. Apart from these localized rearrangements in the vicinity of His 40, the structure of gamma-CHT at pH 2.0 is very similar to that at neutral pH. The structure of gamma-CHT at pH 10.5 is also seen to be almost identical with that at neutral pH. There is no indication that the internal salt bridge between Asp 194 and the alpha-amino group of lle 16 begins to dissociate at pH 10.5. With the exception of the vicinity of His 40, the structure of the bound solvent in the crystal structures at low, neutral and high pH is very similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Literature references that cite this PDB file's key reference

  PubMed id Reference
19549826 E.Zakharova, M.P.Horvath, and D.P.Goldenberg (2009).
Structure of a serine protease poised to resynthesize a peptide bond.
  Proc Natl Acad Sci U S A, 106, 11034-11039.
PDB codes: 3fp6 3fp7 3fp8
19280122 S.J.Abraham, T.Kobayashi, R.J.Solaro, and V.Gaponenko (2009).
Differences in lysine pKa values may be used to improve NMR signal dispersion in reductively methylated proteins.
  J Biomol NMR, 43, 239-246.  
17469803 A.Moulin, J.H.Bell, R.F.Pratt, and D.Ringe (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.
PDB code: 2p8o
16754679 B.Liu, C.J.Schofield, and R.C.Wilmouth (2006).
Structural analyses on intermediates in serine protease catalysis.
  J Biol Chem, 281, 24024-24035.
PDB codes: 2bb4 2bd2 2bd3 2bd4 2bd5 2bd7 2bd8 2bd9 2bda 2bdb 2bdc 2h1u
16636277 E.S.Radisky, J.M.Lee, C.J.Lu, and D.E.Koshland (2006).
Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
  Proc Natl Acad Sci U S A, 103, 6835-6840.
PDB codes: 2age 2agg 2agi 2ah4
14501114 B.V.Prasad, and K.Suguna (2003).
Effect of pH on the structure of rhizopuspepsin.
  Acta Crystallogr D Biol Crystallogr, 59, 1755-1761.
PDB codes: 1uh7 1uh8 1uh9
11856829 R.Berisio, F.Sica, V.S.Lamzin, K.S.Wilson, A.Zagari, and L.Mazzarella (2002).
Atomic resolution structures of ribonuclease A at six pH values.
  Acta Crystallogr D Biol Crystallogr, 58, 441-450.
PDB codes: 1kf2 1kf3 1kf4 1kf5 1kf7 1kf8
9718318 J.Lin, C.S.Cassidy, and P.A.Frey (1998).
Correlations of the basicity of His 57 with transition state analogue binding, substrate reactivity, and the strength of the low-barrier hydrogen bond in chymotrypsin.
  Biochemistry, 37, 11940-11948.  
9843946 J.Lin, W.M.Westler, W.W.Cleland, J.L.Markley, and P.A.Frey (1998).
Fractionation factors and activation energies for exchange of the low barrier hydrogen bonding proton in peptidyl trifluoromethyl ketone complexes of chymotrypsin.
  Proc Natl Acad Sci U S A, 95, 14664-14668.  
9443338 M.M.Krem, and E.Di Cera (1998).
Conserved water molecules in the specificity pocket of serine proteases and the molecular mechanism of Na+ binding.
  Proteins, 30, 34-42.  
9187653 R.C.Wilmouth, I.J.Clifton, C.V.Robinson, P.L.Roach, R.T.Aplin, N.J.Westwood, J.Hajdu, and C.J.Schofield (1997).
Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and porcine pancreatic elastase.
  Nat Struct Biol, 4, 456-462.
PDB code: 1qix
8332606 S.Nakagawa, H.A.Yu, M.Karplus, and H.Umeyama (1993).
Active site dynamics of acyl-chymotrypsin.
  Proteins, 16, 172-194.  
1477273 O.Gursky, J.Badger, Y.Li, and D.L.Caspar (1992).
Conformational changes in cubic insulin crystals in the pH range 7-11.
  Biophys J, 63, 1210-1220.
PDB codes: 1aph 1bph 1cph 1dph
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.