6I0L

Crystal structure of human carbonic anhydrase I in complex with the 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[2-(4-sulfamoylphenyl)ethyl]urea inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Carbonic anhydrase inhibitors based on sorafenib scaffold: Design, synthesis, crystallographic investigation and effects on primary breast cancer cells.

Bozdag, M.Ferraroni, M.Ward, C.Carta, F.Bua, S.Angeli, A.Langdon, S.P.Kunkler, I.H.Al-Tamimi, A.S.Supuran, C.T.

(2019) Eur J Med Chem 182: 111600-111600

  • DOI: https://doi.org/10.1016/j.ejmech.2019.111600
  • Primary Citation of Related Structures:  
    6I0J, 6I0L

  • PubMed Abstract: 

    Carbonic anhydrase inhibitors (CAIs) of the sulfonamide, sulfamate and coumarin classes bearing the phenylureido tail found in the clinically used drug Sorafenib, a multikinase inhibitor actually used for the management of hepatocellular carcinomas, are reported. All compounds were assayed on human (h) CA isoforms I, II, VII and IX, involved in various pathologies. Among the sulfonamides, several compounds were selective for inhibiting hCA IX, with K I values in the low nanomolar ranges (i.e. 0.7-30.2 nM). We explored the binding modes of such compounds by means of X-ray crystallographic studies on isoform hCA I in adduct with one sulfonamide and a sulfamate inhibitor. Antiproliferative properties of some sulfamates on breast tumor cell lines were also investigated.


  • Organizational Affiliation

    University of Florence, NEUROFARBA Dept, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 1
A, B
261Homo sapiensMutation(s): 0 
EC: 4.2.1.1 (PDB Primary Data), 4.2.1.69 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P00915 (Homo sapiens)
Explore P00915 
Go to UniProtKB:  P00915
PHAROS:  P00915
GTEx:  ENSG00000133742 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00915
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GZH (Subject of Investigation/LOI)
Query on GZH

Download Ideal Coordinates CCD File 
D [auth A],
H [auth B]
1-[4-chloranyl-3-(trifluoromethyl)phenyl]-3-[2-(4-sulfamoylphenyl)ethyl]urea
C16 H15 Cl F3 N3 O3 S
FBVAPDWPSNARKD-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
J [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
G [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
F [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.461α = 90
b = 70.453β = 90
c = 121.56γ = 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: 2019-11-20
    Type: Initial release
  • Version 1.1: 2020-12-02
    Changes: Database references, Derived calculations
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Refinement description