5LJT

Crystal structure of human carbonic anhydrase II in complex with the 4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)benzenesulfonamide inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.157 
  • R-Value Work: 0.138 
  • R-Value Observed: 0.139 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Benzenesulfonamides Incorporating Flexible Triazole Moieties Are Highly Effective Carbonic Anhydrase Inhibitors: Synthesis and Kinetic, Crystallographic, Computational, and Intraocular Pressure Lowering Investigations.

Nocentini, A.Ferraroni, M.Carta, F.Ceruso, M.Gratteri, P.Lanzi, C.Masini, E.Supuran, C.T.

(2016) J Med Chem 59: 10692-10704

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b01389
  • Primary Citation of Related Structures:  
    5LJQ, 5LJT

  • PubMed Abstract: 

    Herein we report the synthesis of two series of benzenesulfonamide containing compounds that incorporate the phenyl-1,2,3-triazole moieties. We explored the insertion of appropriate linkers, such as ether, thioether, and amino type, into the inner section of the molecules with the intent to confer additional flexibility. All obtained compounds were screened in vitro as inhibitors of the physiologically relevant human (h) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Many of them were low nanomolar or subnanomolar hCA II, IX, and XII inhibitors, whereas they did not potently inhibit hCA I. Computational and X-ray crystallographic studies of the enzyme-inhibitor adducts helped us to rationalize the obtained results. Some of the sulfonamides reported here showed significant intraocular pressure lowering activity in an animal model of glaucoma.


  • Organizational Affiliation

    Università degli Studi di Firenze , Neurofarba Department., 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 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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
A6N
Query on A6N

Download Ideal Coordinates CCD File 
C [auth A]4-[[4-[azanyl-bis(oxidanyl)-$l^{4}-sulfanyl]phenoxy]methyl]-1-phenyl-1,2,3-triazole
C15 H16 N4 O3 S
CAKKFQLFMKZHOH-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [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
A6N Binding MOAD:  5LJT Ki: 1.2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.157 
  • R-Value Work: 0.138 
  • R-Value Observed: 0.139 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.363α = 90
b = 41.4β = 104.41
c = 72.171γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
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: 2017-06-21
    Type: Initial release
  • Version 1.1: 2024-01-10
    Changes: Data collection, Database references, Refinement description