PDBsum entry 1w1p

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Hydrolase PDB id
Protein chains
498 a.a. *
GOL ×20
GIO ×2
SO4 ×6
Waters ×949
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of s. Marcescens chitinase b in complex with the cyclic dipeptide inhibitor cyclo-(gly-l-pro) at 2.1 a resolution
Structure: Chitinase b. Chain: a, b. Engineered: yes
Source: Serratia marcescens. Organism_taxid: 615. Expressed in: escherichia coli. Expression_system_taxid: 511693.
2.10Å     R-factor:   0.199     R-free:   0.249
Authors: D.R.Houston,B.Synstad,V.G.H.Eijsink,I.Eggleston, D.M.F.Van Aalten
Key ref: D.R.Houston et al. (2004). Structure-based exploration of cyclic dipeptide chitinase inhibitors. J Med Chem, 47, 5713-5720. PubMed id: 15509170 DOI: 10.1021/jm049940a
23-Jun-04     Release date:   10-Jan-05    
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Protein chains
Pfam   ArchSchema ?
Q54276  (Q54276_SERMA) -  Chitinase
499 a.a.
498 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     hydrolase activity     5 terms  


DOI no: 10.1021/jm049940a J Med Chem 47:5713-5720 (2004)
PubMed id: 15509170  
Structure-based exploration of cyclic dipeptide chitinase inhibitors.
D.R.Houston, B.Synstad, V.G.Eijsink, M.J.Stark, I.M.Eggleston, D.M.van Aalten.
Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhibits family 18 chitinases by mimicking the structure of the proposed reaction intermediate. Here we report the high-resolution structures of four new CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro), and cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition, details of enzyme inhibition and in vivo activity against Saccharomyces cerevisiae are presented. The structures reveal that the common cyclo-(Gly-Pro) substructure is sufficient for binding, allowing modification of the side chain of the nonproline residue. This suggests that design of cyclic dipeptides with a view to increasing inhibition of family 18 chitinases should be possible through relatively accessible chemistry. The derivatives presented here in complex with chitinase B from Serratia marcescens provide further insight into the mechanism of inhibition of chitinases by cyclic dipeptides as well as providing a new scaffold for chitinase inhibitor design.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20936530 K.Chanda, C.T.Chou, J.J.Lai, S.F.Lin, G.S.Yellol, and C.M.Sun (2011).
Traceless synthesis of diketopiperazine fused tetrahydro-β-carbolines on soluble polymer support.
  Mol Divers, 15, 569-581.  
19554355 A.Abiram, and P.Kolandaivel (2010).
Structural analysis and the effect of cyclo(His-Pro) dipeptide on neurotoxins--a dynamics and density functional theory study.
  J Mol Model, 16, 193-202.  
20949215 A.Trabocchi, I.Stefanini, M.Morvillo, L.Ciofi, D.Cavalieri, and A.Guarna (2010).
Chemical genetics approach to identify new small molecule modulators of cell growth by phenotypic screening of Saccharomyces cerevisiae strains with a library of morpholine-derived compounds.
  Org Biomol Chem, 8, 5552-5557.  
20871902 A.Znabet, J.Zonneveld, E.Janssen, F.J.De Kanter, M.Helliwell, N.J.Turner, E.Ruijter, and R.V.Orru (2010).
Asymmetric synthesis of synthetic alkaloids by a tandem biocatalysis/Ugi/Pictet-Spengler-type cyclization sequence.
  Chem Commun (Camb), 46, 7706-7708.  
20062868 H.Usuki, Y.Uesugi, J.Arima, Y.Yamamoto, M.Iwabuchi, and T.Hatanaka (2010).
Engineered transaminopeptidase, aminolysin-S for catalysis of peptide bond formation to give linear and cyclic dipeptides by one-pot reaction.
  Chem Commun (Camb), 46, 580-582.  
18680214 C.Petter, C.Scholz, H.Wessner, G.Hansen, P.Henklein, T.Watanabe, and W.Höhne (2008).
Phage display screening for peptidic chitinase inhibitors.
  J Mol Recognit, 21, 401-409.  
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
16953493 J.Saguez, F.Dubois, C.Vincent, J.C.Laberche, B.S.Sangwan-Norreel, and P.Giordanengo (2006).
Differential aphicidal effects of chitinase inhibitors on the polyphagous homopteran Myzus persicae (Sulzer).
  Pest Manag Sci, 62, 1150-1154.  
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.  
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