6D1L

Design, synthesis, and X-ray of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.162 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects.

Angeli, A.di Cesare Mannelli, L.Lucarini, E.Peat, T.S.Ghelardini, C.Supuran, C.T.

(2018) Eur J Med Chem 154: 210-219

  • DOI: https://doi.org/10.1016/j.ejmech.2018.05.026
  • Primary Citation of Related Structures:  
    6D1L, 6D1M

  • PubMed Abstract: 

    A series of selenides bearing benzensulfonamide were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Potent inhibitory action, in the low nanomolar range, was detected against isoforms hCA II and VII, which are known to be involved in neuropathic pain modulation. These selenides showed on the other hand moderate inhibition against the cytosolic isoforms hCA I and transmembrane hCA IX. X-ray crystallographic data of two derivatives bound to hCA II allowed us to rationalize the excellent inhibitory data. In a mice model of neuropathic pain induced by oxaliplatin, some of the strong CA II/VII inhibitors induced a long lasting pain relieving effect.


  • Organizational Affiliation

    Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens)
Explore P00918 
Go to UniProtKB:  P00918
PHAROS:  P00918
GTEx:  ENSG00000104267 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00918
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
FQV Binding MOAD:  6D1L Ki: 7.6 (nM) from 1 assay(s)
BindingDB:  6D1L Ki: 7.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.162 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.327α = 90
b = 41.341β = 104.43
c = 72.08γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-06-13
    Type: Initial release
  • Version 1.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description