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Hydrolase/hydrolase inhibitor PDB id
1o6i
Jmol
Contents
Protein chains
497 a.a. *
Ligands
0HZ ×2
GOL ×31
SO4 ×6
Waters ×1416
* Residue conservation analysis
PDB id:
1o6i
Name: Hydrolase/hydrolase inhibitor
Title: Chitinase b from serratia marcescens complexed with the cata intermediate mimic cyclic dipeptide ci4.
Structure: Chitinase b. Chain: a, b. Engineered: yes
Source: Serratia marcescens. Organism_taxid: 615. Gene: chib. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PDB file)
Resolution:
1.70Å     R-factor:   0.170     R-free:   0.195
Authors: D.R.Houston,I.Eggleston,B.Synstad,V.G.H.Eijsink,D.M.F.Van Aa
Key ref: D.R.Houston et al. (2002). The cyclic dipeptide CI-4 [cyclo-(l-Arg-d-Pro)] inhibits family 18 chitinases by structural mimicry of a reaction intermediate. Biochem J, 368, 23-27. PubMed id: 12323074 DOI: 10.1042/BJ20021034
Date:
03-Oct-02     Release date:   30-Mar-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11797  (CHIB_SERMA) -  Chitinase B
Seq:
Struc: 		499 a.a.
497 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.14  - Chitinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of the 1,4-beta-linkages of N-acetyl-D-glucosamine polymers of chitin.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     carbohydrate metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
DOI no: 10.1042/BJ20021034 Biochem J 368:23-27 (2002)
PubMed id: 12323074  
 
 
The cyclic dipeptide CI-4 [cyclo-(l-Arg-d-Pro)] inhibits family 18 chitinases by structural mimicry of a reaction intermediate.
D.R.Houston, I.Eggleston, B.Synstad, V.G.Eijsink, D.M.van Aalten.
 
  ABSTRACT  
 
Family 18 chitinases are attractive targets for the development of new inhibitors with chemotherapeutic potential against fungi, insects and protozoan/nematodal parasites. Although several inhibitors have been identified, these are based on complex chemistry, which hampers iterative structure-based optimization. Here we report the details of chitinase inhibition by the natural product peptide CI-4 [ cyclo -(L-Arg-D-Pro)], which possesses activity against the human pathogenic fungus Candida albicans, and describe a 1.7 A (0.17 nm) crystal structure of CI-4 in complex with the enzyme. The structure reveals that the cyclic dipeptide inhibits chitinases by structurally mimicking a reaction intermediate, and could, on the basis of its accessible chemistry, be a candidate for further optimization.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20829286 J.Yang, Z.Gan, Z.Lou, N.Tao, Q.Mi, L.Liang, Y.Sun, Y.Guo, X.Huang, C.Zou, Z.Rao, Z.Meng, and K.Q.Zhang (2010).
Crystal structure and mutagenesis analysis of chitinase CrChi1 from the nematophagous fungus Clonostachys rosea in complex with the inhibitor caffeine.
  Microbiology, 156, 3566-3574.
PDB codes: 3g6l 3g6m
18355729 O.A.Andersen, A.Nathubhai, M.J.Dixon, I.M.Eggleston, and D.M.van Aalten (2008).
Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin.
  Chem Biol, 15, 295-301.
PDB codes: 3ch9 3chc 3chd 3che 3chf
17543889 Zaheer-ul-Haq, P.Dalal, N.N.Aronson, and J.D.Madura (2007).
Family 18 chitolectins: comparison of MGP40 and HUMGP39.
  Biochem Biophys Res Commun, 359, 221-226.  
16844689 A.W.Schüttelkopf, O.A.Andersen, F.V.Rao, M.Allwood, C.Lloyd, I.M.Eggleston, and D.M.van Aalten (2006).
Screening-based discovery and structural dissection of a novel family 18 chitinase inhibitor.
  J Biol Chem, 281, 27278-27285.
PDB code: 2iuz
16183021 F.V.Rao, O.A.Andersen, K.A.Vora, J.A.Demartino, and D.M.van Aalten (2005).
Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes.
  Chem Biol, 12, 973-980.
PDB codes: 2a3a 2a3b 2a3c 2a3e
16193156 O.A.Andersen, M.J.Dixon, I.M.Eggleston, and D.M.van Aalten (2005).
Natural product family 18 chitinase inhibitors.
  Nat Prod Rep, 22, 563-579.  
14597613 G.Vaaje-Kolstad, A.Vasella, M.G.Peter, C.Netter, D.R.Houston, B.Westereng, B.Synstad, V.G.Eijsink, and D.M.van Aalten (2004).
Interactions of a family 18 chitinase with the designed inhibitor HM508 and its degradation product, chitobiono-delta-lactone.
  J Biol Chem, 279, 3612-3619.
PDB codes: 1ur8 1ur9
15144973 K.A.Schug, W.Lindner, and K.Lemr (2004).
Isomeric discrimination of arginine-containing dipeptides using electrospray ionization-ion trap mass spectrometry and the kinetic method.
  J Am Soc Mass Spectrom, 15, 840-847.  
12639956 F.V.Rao, D.R.Houston, R.G.Boot, J.M.Aerts, S.Sakuda, and D.M.van Aalten (2003).
Crystal structures of allosamidin derivatives in complex with human macrophage chitinase.
  J Biol Chem, 278, 20110-20116.
PDB codes: 1hki 1hkj 1hkk 1hkm
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.