5FDC

Crystal structure of Human Carbonic Anhydrase II in complex with the anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.170 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies.

Di Fiore, A.De Simone, G.Alterio, V.Riccio, V.Winum, J.Y.Carta, F.Supuran, C.T.

(2016) Org Biomol Chem 14: 4853-4858

  • DOI: https://doi.org/10.1039/c6ob00803h
  • Primary Citation of Related Structures:  
    5FDC, 5FDI

  • PubMed Abstract: 

    JNJ-26990990 ((benzo[b]thien-3-yl)methyl)sulfamide, a sulfamide derivative structurally related to the antiepileptic drug zonisamide, was reported to be devoid of carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties. Here we report that JNJ-26990990 and its S,S-dioxide analog significantly inhibit six human (h) isoforms, hCA I, II, VII, IX, XII and XIV, involved in crucial physiological processes. Inhibition and X-ray crystallographic data for the binding of the two compounds to these enzymes show significant similarity with the zonisamide inhibitory pattern. These findings prompted us to reconsider the structural/pharmacological requirements for designing effective antiepileptics possessing zinc-binding groups of the sulfamide, sulfamate or sulfonamide type in their molecules.


  • Organizational Affiliation

    Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy. gdesimon@unina.it claudiu.supuran@unifi.it.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
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
5WN Binding MOAD:  5FDC Ki: 34.8 (nM) from 1 assay(s)
BindingDB:  5FDC IC50: min: 6.60e+4, max: 1.10e+5 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.170 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.124α = 90
b = 41.427β = 104.34
c = 71.996γ = 90
Software Package:
Software NamePurpose
d*TREKdata reduction
HKL-2000data reduction
HKL-2000data scaling
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-18
    Type: Initial release
  • Version 1.1: 2016-06-01
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Refinement description