3MMF

Crystal structure of human carbonic anhydrase II in complex with a 1,3,5-triazine-substituted benzenesulfonamide inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.182 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.160 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII and XIV over cytosolic isoforms I and II: Solution and X-ray crystallographic studies.

Carta, F.Garaj, V.Maresca, A.Wagner, J.Avvaru, B.S.Robbins, A.H.Scozzafava, A.McKenna, R.Supuran, C.T.

(2011) Bioorg Med Chem 19: 3105-3119

  • DOI: https://doi.org/10.1016/j.bmc.2011.04.005
  • Primary Citation of Related Structures:  
    3MMF, 3MNA

  • PubMed Abstract: 

    Reaction of cyanuryl chloride with d,l-amino acids and amino alcohols afforded a new series of triazinyl-substituted benzenesulfonamides incorporating amino acyl/hydroxyalkyl-amino moieties. Inhibition studies of physiologically relevant human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, such as CA I, II, IX, XII and XIV with these compounds are reported. They showed moderate-weak inhibition of the cytosolic, offtarget isozymes CA I and II, but many of them were low nanomolar inhibitors of the transmembrane, tumor-associated CA IX and XII (and also of CA XIV). The X-ray crystal structure of two of these compounds in adduct with CA II allowed us to understand the features associated with this strong inhibitory properties and possibly also their selectivity. Two of these compounds were also investigated for the inhibition of other human isoforms, that is, hCA IV, VA, VB, VI, VII and XIII, as well as inhibitors of the fungal pathogenic CAs Nce103 (Candida albicans) and Can2 (Cryptococcus neoformans), showing interesting activity. The 1,3,5-triazinyl-substituted benzenesulfonamides constitute thus a class of compounds with great potential for obtaining inhibitors targeting both α-class mammalian, tumor-associated, and β-class from pathogenic organisms CAs.


  • Organizational Affiliation

    Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Florence, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2HCA2
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
D9H
Query on D9H

Download Ideal Coordinates CCD File 
C [auth A]4-({4-chloro-6-[(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonamide
C11 H13 Cl N6 O3 S
QZIFPRRIFLBFHT-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
D9H PDBBind:  3MMF Ki: 37 (nM) from 1 assay(s)
Binding MOAD:  3MMF Ki: 37 (nM) from 1 assay(s)
BindingDB:  3MMF Ki: 37 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.182 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.160 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.336α = 90
b = 41.242β = 104.31
c = 72.05γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description