1W9P

Specificity and affinity of natural product cyclopentapeptide inhibitors against Aspergillus fumigatus, human and bacterial chitinaseFra


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Specificity and Affinity of Natural Product Cyclopentapeptide Inhibitors Against Aspergillus Fumigatus, Human and Bacterial Chitinases

Rao, F.V.Houston, D.R.Boot, R.G.Aerts, J.M.F.G.Hodkinson, M.Adams, D.J.Shiomi, K.Omura, S.Van Aalten, D.M.F.

(2005) Chem Biol 12: 65

  • DOI: https://doi.org/10.1016/j.chembiol.2004.10.013
  • Primary Citation of Related Structures:  
    1W9P, 1W9U, 1W9V, 1WAW, 1WB0

  • PubMed Abstract: 

    Family 18 chitinases play key roles in organisms ranging from bacteria to man. There is a need for specific, potent inhibitors to probe the function of these chitinases in different organisms. Such molecules could also provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural product peptides, argifin and argadin, have been characterized, which structurally mimic chitinase-chitooligosaccharide interactions and inhibit a bacterial chitinase in the nM-mM range. Here, we show that these inhibitors also act on human and Aspergillus fumigatus chitinases. The structures of these enzymes in complex with argifin and argadin, together with mutagenesis, fluorescence, and enzymology, reveal that subtle changes in the binding site dramatically affect affinity and selectivity. The data show that it may be possible to develop specific chitinase inhibitors based on the argifin/argadin scaffolds.


  • Organizational Affiliation

    Division of Biological Chemistry & Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CHITINASE
A, B
433Aspergillus fumigatusMutation(s): 0 
EC: 3.2.1.14
UniProt
Find proteins for Q873X9 (Aspergillus fumigatus)
Explore Q873X9 
Go to UniProtKB:  Q873X9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ873X9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.181 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.407α = 90
b = 117.407β = 90
c = 99.27γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-10-29
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description