3CHC

Crystal structure of Aspergillus fumigatus chitinase B1 in complex with monopeptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.166 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin.

Andersen, O.A.Nathubhai, A.Dixon, M.J.Eggleston, I.M.van Aalten, D.M.

(2008) Chem Biol 15: 295-301

  • DOI: https://doi.org/10.1016/j.chembiol.2008.02.015
  • Primary Citation of Related Structures:  
    3CH9, 3CHC, 3CHD, 3CHE, 3CHF

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Division of Biological Chemistry & Drug Discovery, College 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 
Gene Names: chiB1
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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZRG
Query on ZRG

Download Ideal Coordinates CCD File 
H [auth A],
O [auth B]
(2S)-2-acetamido-N-methyl-5-[[N-(methylcarbamoyl)carbamimidoyl]amino]pentanamide
C11 H22 N6 O3
IHUKVJKKTBLTEE-QMMMGPOBSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
I [auth B],
J [auth B],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
ZRG Binding MOAD:  3CHC IC50: 8.10e+4 (nM) from 1 assay(s)
PDBBind:  3CHC IC50: 8.10e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.166 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.183α = 90
b = 117.183β = 90
c = 100.045γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
PHASESphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description