1LQ0

CRYSTAL STRUCTURE OF HUMAN CHITOTRIOSIDASE AT 2.2 ANGSTROM RESOLUTION


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.212 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of human chitotriosidase. Implications for specific inhibitor design and function of mammalian chitinase-like lectins

Fusetti, F.Von Moeller, H.Houston, D.Rozeboom, H.J.Dijkstra, B.W.Boot, R.G.Aerts, J.M.Van Aalten, D.M.

(2002) J Biol Chem 277: 25537-25544

  • DOI: https://doi.org/10.1074/jbc.M201636200
  • Primary Citation of Related Structures:  
    1GUV, 1LG1, 1LG2, 1LQ0

  • PubMed Abstract: 

    Chitin hydrolases have been identified in a variety of organisms ranging from bacteria to eukaryotes. They have been proposed to be possible targets for the design of novel chemotherapeutics against human pathogens such as fungi and protozoan parasites as mammals were not thought to possess chitin-processing enzymes. Recently, a human chitotriosidase was described as a marker for Gaucher disease with plasma levels of the enzyme elevated up to 2 orders of magnitude. The chitotriosidase was shown to be active against colloidal chitin and is inhibited by the family 18 chitinase inhibitor allosamidin. Here, the crystal structure of the human chitotriosidase and complexes with a chitooligosaccharide and allosamidin are described. The structures reveal an elongated active site cleft, compatible with the binding of long chitin polymers, and explain the inactivation of the enzyme through an inherited genetic deficiency. Comparison with YM1 and HCgp-39 shows how the chitinase has evolved into these mammalian lectins by the mutation of key residues in the active site, tuning the substrate binding specificity. The soaking experiments with allosamidin and chitooligosaccharides give insight into ligand binding properties and allow the evaluation of differential binding and design of species-selective chitinase inhibitors.


  • Organizational Affiliation

    Laboratory of Biophysical Chemistry, University of Groningen, The Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CHITOTRIOSIDASE365Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13231 (Homo sapiens)
Explore Q13231 
Go to UniProtKB:  Q13231
PHAROS:  Q13231
GTEx:  ENSG00000133063 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13231
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.212 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.45α = 90
b = 93.45β = 90
c = 89.62γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-07-29
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance