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PDBsum entry 1h9h
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protein metals Protein-protein interface(s) links
Hydrolase inhibitor PDB id
1h9h

 

 

 

 

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Contents
Protein chains
231 a.a. *
32 a.a. *
Metals
_CA
Waters ×177
* Residue conservation analysis
PDB id:
1h9h
Name: Hydrolase inhibitor
Title: Complex of eeti-ii with porcine trypsin
Structure: Trypsin. Chain: e. Trypsin inhibitor ii. Chain: i. Synonym: eeti-ii. Engineered: yes. Mutation: yes. Other_details: c-terminal tag of 6 histidines
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas. Secretion: saliva. Other_details: sigma. Synthetic: yes. Ecballium elaterium. Squirting cucumber.
Biol. unit: Dimer (from PDB file)
Resolution:
1.50Å     R-factor:   0.235     R-free:   0.276
Authors: R.Kraetzner,A.Wentzel,H.Kolmar,I.Uson
Key ref:
R.Krätzner et al. (2005). Structure of Ecballium elaterium trypsin inhibitor II (EETI-II): a rigid molecular scaffold. Acta Crystallogr D Biol Crystallogr, 61, 1255-1262. PubMed id: 16131759 DOI: 10.1107/S0907444905021207
Date:
12-Mar-01     Release date:   26-Jul-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00761  (TRYP_PIG) -  Trypsin from Sus scrofa
Seq:
Struc: 		231 a.a.
231 a.a.*
Protein chain
Pfam   ArchSchema ?
P12071  (ITR2_ECBEL) -  Trypsin inhibitor 2 from Ecballium elaterium
Seq:
Struc: 		30 a.a.
32 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 11 residue positions (black crosses)

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

 

 
DOI no: 10.1107/S0907444905021207 Acta Crystallogr D Biol Crystallogr 61:1255-1262 (2005)
PubMed id: 16131759  
 
 
Structure of Ecballium elaterium trypsin inhibitor II (EETI-II): a rigid molecular scaffold.
R.Krätzner, J.E.Debreczeni, T.Pape, T.R.Schneider, A.Wentzel, H.Kolmar, G.M.Sheldrick, I.Uson.
 
  ABSTRACT  
 
The Ecballium elaterium trypsin inhibitor II (EETI-II) belongs to the family of squash inhibitors and is one of the strongest inhibitors known for trypsin. The eight independent molecules of EETI-II in the crystal structure reported here provide a good opportunity to test the hypothesis that this small cystine-knot protein (knottin) is sufficiently rigid to be used as a molecular scaffold for protein-engineering purposes. To extend this test, the structures of two complexes of EETI-II with trypsin have also been determined, one carrying a four-amino-acid mutation of EETI-II. The remarkable similarity of these structures confirms the rigidity of the molecular framework and hence its suitability as a molecular scaffold.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Dimer formed by the molecules A and B. Molecule pairs CD and EF display a similar arrangement. The sodium ion is shown as a solid ball. 		Figure 6.
Figure 6 Least-squares superpositions of all main-chain atoms of EETI-II. (a) All eight independent molecules in the uncomplexed structure; (b) uncomplexed (black) and complexed (red) EETI-II and the NMR model (green); (c) uncomplexed EETI-II (black), the trypsin-EETI-II- [beta] TNNK complex (red) and CMTI-I (blue).
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 1255-1262) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19368895 H.J.Chang, H.J.Hsu, C.F.Chang, H.P.Peng, Y.K.Sun, H.M.Yu, H.C.Shih, C.Y.Song, Y.T.Lin, C.C.Chen, C.H.Wang, and A.S.Yang (2009).
Molecular evolution of cystine-stabilized miniproteins as stable proteinaceous binders.
  Structure, 17, 620-631.  
19780078 J.Austin, W.Wang, S.Puttamadappa, A.Shekhtman, and J.A.Camarero (2009).
Biosynthesis and biological screening of a genetically encoded library based on the cyclotide MCoTI-I.
  Chembiochem, 10, 2663-2670.  
19730675 J.L.Lahti, A.P.Silverman, and J.R.Cochran (2009).
Interrogating and predicting tolerated sequence diversity in protein folds: application to E. elaterium trypsin inhibitor-II cystine-knot miniprotein.
  PLoS Comput Biol, 5, e1000499.  
19452550 R.H.Kimura, A.M.Levin, F.V.Cochran, and J.R.Cochran (2009).
Engineered cystine knot peptides that bind alphavbeta3, alphavbeta5, and alpha5beta1 integrins with low-nanomolar affinity.
  Proteins, 77, 359-369.  
19077275 A.Heitz, O.Avrutina, D.Le-Nguyen, U.Diederichsen, J.F.Hernandez, J.Gracy, H.Kolmar, and L.Chiche (2008).
Knottin cyclization: Impact on Structure and Dynamics.
  BMC Struct Biol, 8, 54.  
18435757 H.Kolmar (2008).
Alternative binding proteins: biological activity and therapeutic potential of cystine-knot miniproteins.
  FEBS J, 275, 2684-2690.  
17619117 M.Werle, H.Kolmar, R.Albrecht, and A.Bernkop-Schnürch (2008).
Characterisation of the barrier caused by luminally secreted gastro-intestinal proteolytic enzymes for two novel cystine-knot microproteins.
  Amino Acids, 35, 195-200.  
18058774 O.Avrutina, H.U.Schmoldt, D.Gabrijelcic-Geiger, A.Wentzel, H.Frauendorf, C.P.Sommerhoff, U.Diederichsen, and H.Kolmar (2008).
Head-to-tail cyclized cystine-knot peptides by a combined recombinant and chemical route of synthesis.
  Chembiochem, 9, 33-37.  
16547012 M.Cemazar, N.L.Daly, S.Häggblad, K.P.Lo, E.Yulyaningsih, and D.J.Craik (2006).
Knots in rings. The circular knotted protein Momordica cochinchinensis trypsin inhibitor-II folds via a stable two-disulfide intermediate.
  J Biol Chem, 281, 8224-8232.  
16336125 O.Avrutina, H.U.Schmoldt, D.Gabrijelcic-Geiger, D.Le Nguyen, C.P.Sommerhoff, U.Diederichsen, and H.Kolmar (2005).
Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II.
  Biol Chem, 386, 1301-1306.  
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.

 

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