3VBD

Complex of human carbonic anhydrase II with 4-(6-methoxy-3,4-dihydroisoquinolin-1-yl)benzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.05 Å
  • R-Value Free: 0.160 
  • R-Value Work: 0.127 
  • R-Value Observed: 0.134 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Synthesis, Structure-Activity Relationship Studies, and X-ray Crystallographic Analysis of Arylsulfonamides as Potent Carbonic Anhydrase Inhibitors.

Gitto, R.Damiano, F.M.Mader, P.De Luca, L.Ferro, S.Supuran, C.T.Vullo, D.Brynda, J.Rezacova, P.Chimirri, A.

(2012) J Med Chem 55: 3891-3899

  • DOI: https://doi.org/10.1021/jm300112w
  • Primary Citation of Related Structures:  
    3V7X, 3VBD

  • PubMed Abstract: 

    A series of arylsulfonamides has been synthesized and investigated for the inhibition of some selected human carbonic anhydrase isoforms. The studied compounds showed significant inhibitory effects in the nanomolar range toward druggable isoforms (hCA VII, hCA IX, and hCA XIV) (K(i) values from 4.8 to 61.7 nM), whereas they generally exhibited significant selectivity over hCA I and hCA II, that are ubiquitous and considered off-target isoforms. On the basis of biochemical data, we herein discussed structure-affinity relationships for this series of arylsulfonamides, suggesting a key role for alkoxy substituents in CA inhibition. Furthermore, X-ray crystal structures of complexes of two active inhibitors (I and 2a) with hCA II allowed us to elucidate the main interactions between the inhibitor and specific amino acid residues within the catalytic site.


  • Organizational Affiliation

    Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, I-98168 Messina, Italy. rgitto@unime.it


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2259Homo 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
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
0FZ Binding MOAD:  3VBD Ki: 8.6 (nM) from 1 assay(s)
PDBBind:  3VBD Ki: 8.6 (nM) from 1 assay(s)
BindingDB:  3VBD Ki: 8.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.05 Å
  • R-Value Free: 0.160 
  • R-Value Work: 0.127 
  • R-Value Observed: 0.134 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.01α = 90
b = 41.18β = 104.33
c = 71.76γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
SHELXL-97refinement
MOSFLMdata reduction
SCALAdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-04
    Type: Initial release
  • Version 1.1: 2012-04-11
    Changes: Database references
  • Version 1.2: 2012-06-27
    Changes: Database references
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations