3ARV

Crystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - complex structure with Sanguinarine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.177 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.146 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Potent family-18 chitinase inhibitors: x-ray structures, affinities, and binding mechanisms

Pantoom, S.Vetter, I.R.Prinz, H.Suginta, W.

(2011) J Biol Chem 286: 24312-24323

  • DOI: https://doi.org/10.1074/jbc.M110.183376
  • Primary Citation of Related Structures:  
    3ARO, 3ARP, 3ARQ, 3ARR, 3ARS, 3ART, 3ARU, 3ARV, 3ARW, 3ARX, 3ARY, 3ARZ, 3AS0, 3AS1, 3AS2, 3AS3

  • PubMed Abstract: 

    Six novel inhibitors of Vibrio harveyi chitinase A (VhChiA), a family-18 chitinase homolog, were identified by in vitro screening of a library of pharmacologically active compounds. Unlike the previously identified inhibitors that mimicked the reaction intermediates, crystallographic evidence from 14 VhChiA-inhibitor complexes showed that all of the inhibitor molecules occupied the outer part of the substrate-binding cleft at two hydrophobic areas. The interactions at the aglycone location are well defined and tightly associated with Trp-397 and Trp-275, whereas the interactions at the glycone location are patchy, indicating lower affinity and a loose interaction with two consensus residues, Trp-168 and Val-205. When Trp-275 was substituted with glycine (W275G), the binding affinity toward all of the inhibitors dramatically decreased, and in most structures two inhibitor molecules were found to stack against Trp-397 at the aglycone site. Such results indicate that hydrophobic interactions are important for binding of the newly identified inhibitors by the chitinase. X-ray data and isothermal microcalorimetry showed that the inhibitors occupied the active site of VhChiA in three different binding modes, including single-site binding, independent two-site binding, and sequential two-site binding. The inhibitory effect of dequalinium in the low nanomolar range makes this compound an extremely attractive lead compound for plausible development of therapeutics against human diseases involving chitinase-mediated pathologies.


  • Organizational Affiliation

    Biochemistry-Electrochemistry Research Unit, School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chitinase A584Vibrio harveyiMutation(s): 0 
Gene Names: CHIA
EC: 3.2.1.14
UniProt
Find proteins for Q9AMP1 (Vibrio harveyi)
Explore Q9AMP1 
Go to UniProtKB:  Q9AMP1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9AMP1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.177 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.146 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.23α = 90
b = 50.82β = 99.49
c = 93.39γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-01-29
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description