3V7X

Complex of human carbonic anhydrase II with N-[2-(3,4-dimethoxyphenyl)ethyl]-4-sulfamoylbenzamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.03 Å
  • R-Value Free: 0.148 
  • R-Value Work: 0.117 
  • R-Value Observed: 0.117 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


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
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
D7A
Query on D7A

Download Ideal Coordinates CCD File 
C [auth A]N-[2-(3,4-dimethoxyphenyl)ethyl]-4-sulfamoylbenzamide
C17 H20 N2 O5 S
ZVVZHSQXKXOTQG-UHFFFAOYSA-N
MBO
Query on MBO

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A],
K [auth A],
L [auth A]
MERCURIBENZOIC ACID
C7 H5 Hg O2
FVFZSVRSDNUCGG-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
D7A BindingDB:  3V7X Ki: 2.7 (nM) from 1 assay(s)
Binding MOAD:  3V7X Ki: 2.7 (nM) from 1 assay(s)
PDBBind:  3V7X Ki: 2.7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.03 Å
  • R-Value Free: 0.148 
  • R-Value Work: 0.117 
  • R-Value Observed: 0.117 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.14α = 90
b = 41.51β = 104.23
c = 71.84γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SHELXL-97refinement
HKL-3000data reduction
HKL-3000data scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


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: 2023-09-13
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description