PDBsum entry 3chd

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Hydrolase/hydrolase inhibitor PDB id
Protein chains
395 a.a. *
WRG ×2
SO4 ×14
Waters ×827
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of aspergillus fumigatus chitinase b1 in c with dipeptide
Structure: Chitinase. Chain: a, b. Synonym: class v chitinase chib1. Engineered: yes
Source: Aspergillus fumigatus. Organism_taxid: 5085. Gene: chib1, afua_8g01410. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.00Å     R-factor:   0.177     R-free:   0.215
Authors: O.A.Andersen,D.M.F.Van Aalten
Key ref: O.A.Andersen et al. (2008). Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin. Chem Biol, 15, 295-301. PubMed id: 18355729
09-Mar-08     Release date:   25-Mar-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q873X9  (Q873X9_ASPFM) -  Endochitinase B1
433 a.a.
395 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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!
  Biological process     carbohydrate metabolic process   2 terms 
  Biochemical function     hydrolase activity, hydrolyzing O-glycosyl compounds     2 terms  


Chem Biol 15:295-301 (2008)
PubMed id: 18355729  
Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin.
O.A.Andersen, A.Nathubhai, M.J.Dixon, I.M.Eggleston, D.M.van Aalten.
Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides, and antiasthmatics. Argifin, a natural product cyclopentapeptide, competitively inhibits family 18 chitinases in the nanomolar to micromolar range and shows extensive substrate mimicry. In an attempt to map the active fragments of this large natural product, the cyclopentapeptide was progressively dissected down to four linear peptides and dimethylguanylurea, synthesized using a combination of solution and solid phase peptide synthesis. The peptide fragments inhibit chitinase B1 from Aspergillus fumigatus (AfChiB1), the human chitotriosidase, and chitinase activity in lung homogenates from a murine model of chronic asthma, with potencies ranging from high nanomolar to high micromolar inhibition. X-ray crystallographic analysis of the chitinase-inhibitor complexes revealed that the conformations of the linear peptides were remarkably similar to that of the natural product. Strikingly, the dimethylguanylurea fragment, representing only a quarter of the natural product mass, was found to harbor all significant interactions with the protein and binds with unusually high efficiency. The data provide useful information that could lead to the generation of drug-like, natural product-based chitinase inhibitors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20826216 E.R.Goedken, R.F.O'Brien, T.Xiang, D.L.Banach, S.C.Marchie, E.H.Barlow, S.Hubbard, J.A.Mankovich, J.Jiang, P.L.Richardson, C.A.Cuff, and A.D.Cherniack (2011).
Functional comparison of recombinant acidic mammalian chitinase with enzyme from murine bronchoalveolar lavage.
  Protein Expr Purif, 75, 55-62.  
20727982 C.Abad-Zapatero, O.Perišić, J.Wass, A.P.Bento, J.Overington, B.Al-Lazikani, and M.E.Johnson (2010).
Ligand efficiency indices for an effective mapping of chemico-biological space: the concept of an atlas-like representation.
  Drug Discov Today, 15, 804-811.  
21168763 C.L.Rush, A.W.Schüttelkopf, R.Hurtado-Guerrero, D.E.Blair, A.F.Ibrahim, S.Desvergnes, I.M.Eggleston, and D.M.van Aalten (2010).
Natural product-guided discovery of a fungal chitinase inhibitor.
  Chem Biol, 17, 1275-1281.
PDB codes: 2xuc 2xvn 2xvp
19109670 M.J.Dixon, A.Nathubhai, O.A.Andersen, D.M.van Aalten, and I.M.Eggleston (2009).
Solid-phase synthesis of cyclic peptide chitinase inhibitors: SAR of the argifin scaffold.
  Org Biomol Chem, 7, 259-268.  
19097997 R.Hurtado-Guerrero, A.W.Schüttelkopf, I.Mouyna, A.F.Ibrahim, S.Shepherd, T.Fontaine, J.P.Latgé, and D.M.van Aalten (2009).
Molecular mechanisms of yeast cell wall glucan remodeling.
  J Biol Chem, 284, 8461-8469.
PDB codes: 2w61 2w62 2w63
19329983 T.Hirose, T.Sunazuka, A.Sugawara, A.Endo, K.Iguchi, T.Yamamoto, H.Ui, K.Shiomi, T.Watanabe, K.B.Sharpless, and S.Omura (2009).
Chitinase inhibitors: extraction of the active framework from natural argifin and use of in situ click chemistry.
  J Antibiot (Tokyo), 62, 277-282.  
18558099 D.J.Vocadlo, and G.J.Davies (2008).
Mechanistic insights into glycosidase chemistry.
  Curr Opin Chem Biol, 12, 539-555.  
19568802 H.Prinz, and A.Schönichen (2008).
Transient binding patches: a plausible concept for drug binding.
  J Chem Biol, 1, 95.  
18355718 H.Prinz (2008).
How to identify a pharmacophore.
  Chem Biol, 15, 207-208.  
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.