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PDBsum entry 2er9
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Hydrolase-hydrolase inhibitor PDB id
2er9

 

 

 

 

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Contents
Protein chain
330 a.a. *
Ligands
BOC-HIS-PRO-PHE-
HIS-STA-LEU-PHE
Waters ×322
* Residue conservation analysis
PDB id:
2er9
Name: Hydrolase-hydrolase inhibitor
Title: X-ray studies of aspartic proteinase-statine inhibitor complexes.
Structure: Endothiapepsin. Chain: e. Engineered: yes. L363,564. Chain: i. Engineered: yes
Source: Cryphonectria parasitica. Chestnut blight fungus. Organism_taxid: 5116. Synthetic: yes
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.170    
Authors: J.B.Cooper,S.I.Foundling,J.Boger,T.L.Blundell
Key ref:
J.B.Cooper et al. (1989). X-ray studies of aspartic proteinase-statine inhibitor complexes. Biochemistry, 28, 8596-8603. PubMed id: 2690945 DOI: 10.1021/bi00447a049
Date:
20-Oct-90     Release date:   15-Jan-91    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11838  (CARP_CRYPA) -  Endothiapepsin from Cryphonectria parasitica
Seq:
Struc: 		419 a.a.
330 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.23.22  - endothiapepsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1', but does not cleave 14-Ala-|-Leu-15 in the B chain of insulin or Z-Glu-Tyr. Clots milk.

 

 
DOI no: 10.1021/bi00447a049 Biochemistry 28:8596-8603 (1989)
PubMed id: 2690945  
 
 
X-ray studies of aspartic proteinase-statine inhibitor complexes.
J.B.Cooper, S.I.Foundling, T.L.Blundell, J.Boger, R.A.Jupp, J.Kay.
 
  ABSTRACT  
 
The conformation of a statine-containing renin inhibitor complexed with the aspartic proteinase from the fungus Endothia parasitica (EC 3.4.23.6) has been determined by X-ray diffraction at 2.2-A resolution (R = 0.17). We describe the structure of the complex at high resolution and compare this with a 3.0-A resolution analysis of a bound inhibitor, L-364,099, containing a cyclohexylalanine analogue of statine. The inhibitors bind in extended conformations in the long active-site cleft, and the hydroxyl of the transition-state analogue, statine, interacts strongly with the catalytic aspartates via hydrogen bonds to the essential carboxyl groups. This work provides a detailed structural analysis of the role of statine in peptide inhibitors. It shows conclusively that statine should be considered a dipeptide analogue (occupying P1 to P1') despite lacking the equivalent of a P1' side chain, although other inhibitor residues (especially P2) may compensate by interacting at the unoccupied S1' specificity subsite.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
16972793 F.Majer, L.Pavlícková, P.Majer, M.Hradilek, E.Dolejsí, O.Hrusková-Heidingsfeldová, and I.Pichová (2006).
Structure-based specificity mapping of secreted aspartic proteases of Candida parapsilosis, Candida albicans, and Candida tropicalis using peptidomimetic inhibitors and homology modeling.
  Biol Chem, 387, 1247-1254.  
15039581 M.O.Badasso, V.Dhanaraj, S.P.Wood, J.B.Cooper, and T.L.Blundell (2004).
Crystallization and X-ray analysis of the Y75N mutant of Mucor pusillus pepsin complexed with inhibitor.
  Acta Crystallogr D Biol Crystallogr, 60, 770-772.  
11714911 N.S.Andreeva, and L.D.Rumsh (2001).
Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes.
  Protein Sci, 10, 2439-2450.  
10089458 J.Yang, and J.W.Quail (1999).
Structure of the Rhizomucor miehei aspartic proteinase complexed with the inhibitor pepstatin A at 2.7 A resolution.
  Acta Crystallogr D Biol Crystallogr, 55, 625-630.
PDB code: 2rmp
9228062 T.Shintani, K.Nomura, and E.Ichishima (1997).
Engineering of porcine pepsin. Alteration of S1 substrate specificity of pepsin to those of fungal aspartic proteinases by site-directed mutagenesis.
  J Biol Chem, 272, 18855-18861.  
7561976 C.McMartin, and R.S.Bohacek (1995).
Flexible matching of test ligands to a 3D pharmacophore using a molecular superposition force field: comparison of predicted and experimental conformations of inhibitors of three enzymes.
  J Comput Aided Mol Des, 9, 237-250.  
  7703859 D.Bailey, and J.B.Cooper (1994).
A structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica.
  Protein Sci, 3, 2129-2143.
PDB codes: 1epl 1epm 1epn 1epr 1eqs
8483337 R.A.Wiley, and D.H.Rich (1993).
Peptidomimetics derived from natural products.
  Med Res Rev, 13, 327-384.  
8259000 S.S.Abdel-Meguid (1993).
Inhibitors of aspartyl proteinases.
  Med Res Rev, 13, 731-778.  
1603805 A.Sali, B.Veerapandian, J.B.Cooper, D.S.Moss, T.Hofmann, and T.L.Blundell (1992).
Domain flexibility in aspartic proteinases.
  Proteins, 12, 158-170.  
  1304340 B.Veerapandian, J.B.Cooper, A.Sali, T.L.Blundell, R.L.Rosati, B.W.Dominy, D.B.Damon, and D.J.Hoover (1992).
Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases.
  Protein Sci, 1, 322-328.
PDB code: 1epo
1765127 R.J.Breckenridge (1991).
Molecular recognition: models for drug design.
  Experientia, 47, 1148-1161.  
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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