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PDBsum entry 1amh
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protein metals Protein-protein interface(s) links
Hydrolase PDB id
1amh

 

 

 

 

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Contents
Protein chains
223 a.a. *
Metals
_CA ×2
Waters ×128
* Residue conservation analysis
PDB id:
1amh
Name: Hydrolase
Title: Uncomplexed rat trypsin mutant with asp 189 replaced with ser (d189s)
Structure: Anionic trypsin. Chain: a, b. Engineered: yes. Mutation: yes
Source: Rattus rattus. Black rat. Organism_taxid: 10117. Organ: pancreas. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.182     R-free:   0.242
Authors: E.Szabo,Z.S.Bocskei,G.Naray-Szabo,L.Graf
Key ref: E.Szabó et al. (1999). The three-dimensional structure of Asp189Ser trypsin provides evidence for an inherent structural plasticity of the protease. Eur J Biochem, 263, 20-26. PubMed id: 10429182
Date:
17-Jun-97     Release date:   24-Dec-97    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00763  (TRY2_RAT) -  Anionic trypsin-2 from Rattus norvegicus
Seq:
Struc: 		246 a.a.
223 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.4  - trypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

 

 
Eur J Biochem 263:20-26 (1999)
PubMed id: 10429182  
 
 
The three-dimensional structure of Asp189Ser trypsin provides evidence for an inherent structural plasticity of the protease.
E.Szabó, Z.Böcskei, G.Náray-Szabó, L.Gráf.
 
  ABSTRACT  
 
Trypsin mutant Asp189Ser, first described by Gráf et al. [Gráf, L., Jancsó, A., Szilágyi, L., Hegyi, G., Pintér, K., Náray-Szabó, G., Hepp, J., Medzihradszky, K. & Rutter, W.J. (1988) Proc. Natl Acad. Sci. USA 85, 4961-4965] has played an important role in recent studies on the structural basis of substrate-specific catalysis by serine proteases. The present work reports the three-dimensional structure of this mutant crystallized in unliganded form: the first unliganded rat trypsin structure reported. The X-ray structure of the Asp189Ser trypsin mutant in complex with bovine pancreatic trypsin inhibitor is already known. The X-ray structure of free Asp189Ser rat trypsin revealed that the single amino acid mutation at the bottom of the substrate binding pocket of trypsin resulted in extensive structural changes around the mutated site and in dimerization of the mutant, in contrast with the complexed enzyme the structure of which is practically the same as that of wild-type trypsin. The structural rearrangement in the mutant was shown to be restricted to the activation domain region providing further evidence for the allosteric property of this structural-functional unit of the enzyme. This study supports our view that the plasticity of the activation domain may play an important role in the mechanism of substrate-specific serine protease action.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
17805946 B.Jelinek, G.Katona, K.Fodor, I.Venekei, and L.Gráf (2008).
The crystal structure of a trypsin-like mutant chymotrypsin: the role of position 226 in the activity and specificity of S189D chymotrypsin.
  Protein J, 27, 79-87.
PDB code: 2jet
17531094 A.Del Sol, M.J.Araúzo-Bravo, D.Amoros, and R.Nussinov (2007).
Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages.
  Genome Biol, 8, R92.  
16738564 A.del Sol, H.Fujihashi, D.Amoros, and R.Nussinov (2006).
Residues crucial for maintaining short paths in network communication mediate signaling in proteins.
  Mol Syst Biol, 2, 2006.0019.  
16358328 P.Hudáky, and A.Perczel (2006).
A self-stabilized model of the chymotrypsin catalytic pocket. The energy profile of the overall catalytic cycle.
  Proteins, 62, 749-759.  
15840825 H.R.Maun, C.Eigenbrot, H.Raab, D.Arnott, L.Phu, S.Bullens, and R.A.Lazarus (2005).
Disulfide locked variants of factor VIIa with a restricted beta-strand conformation have enhanced enzymatic activity.
  Protein Sci, 14, 1171-1180.  
15923233 W.Ma, C.Tang, and L.Lai (2005).
Specificity of trypsin and chymotrypsin: loop-motion-controlled dynamic correlation as a determinant.
  Biophys J, 89, 1183-1193.  
14679197 S.Prasad, A.M.Cantwell, L.A.Bush, P.Shih, H.Xu, and E.Di Cera (2004).
Residue Asp-189 controls both substrate binding and the monovalent cation specificity of thrombin.
  J Biol Chem, 279, 10103-10108.  
12483203 G.M.Süel, S.W.Lockless, M.A.Wall, and R.Ranganathan (2003).
Evolutionarily conserved networks of residues mediate allosteric communication in proteins.
  Nat Struct Biol, 10, 59-69.  
11106412 R.Grünberg, I.Domgall, R.Günther, K.Rall, H.J.Hofmann, and F.Bordusa (2000).
Peptide bond formation mediated by substrate mimetics. Structure-guidedoptimization of trypsin for synthesis.
  Eur J Biochem, 267, 7024-7030.  
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.

 

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