5E2S

Crystal structure of human carbonic anhydrase II in complex with the 4-(2-iso-propylphenyl)benzenesulfonamide inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 

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This is version 1.2 of the entry. See complete history


Literature

4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki-Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies.

Cornelio, B.Laronze-Cochard, M.Ceruso, M.Ferraroni, M.Rance, G.A.Carta, F.Khlobystov, A.N.Fontana, A.Supuran, C.T.Sapi, J.

(2016) J Med Chem 59: 721-732

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01771
  • Primary Citation of Related Structures:  
    5E28, 5E2K, 5E2S

  • PubMed Abstract: 

    Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.


  • Organizational Affiliation

    Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 Rue Cognacq-Jay, F-51096 Reims Cedex, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2258Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5CX
Query on 5CX

Download Ideal Coordinates CCD File 
C [auth A]2'-(propan-2-yl)biphenyl-4-sulfonamide
C15 H17 N O2 S
IRABTZHXKCTBRE-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
5CX Binding MOAD:  5E2S Ki: 0.98 (nM) from 1 assay(s)
BindingDB:  5E2S Ki: 0.98 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.251α = 90
b = 41.296β = 104.34
c = 71.923γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-01-20
    Type: Initial release
  • Version 1.1: 2016-02-10
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Refinement description