4KNM

Crystal structure of human carbonic anhydrase isozyme XIII with 2-Chloro-4-{[(4,6-dimethylpyrimidin-2-yl)sulfanyl]acetyl}benzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.184 

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This is version 1.1 of the entry. See complete history


Literature

Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII

Capkauskaite, E.Zubriene, A.Smirnov, A.Torresan, J.Kisonaite, M.Kazokaite, J.Gylyte, J.Michailoviene, V.Jogaite, V.Manakova, E.Grazulis, S.Tumkevicius, S.Matulis, D.

(2013) Bioorg Med Chem 21: 6937-6947

  • DOI: https://doi.org/10.1016/j.bmc.2013.09.029
  • Primary Citation of Related Structures:  
    4KNI, 4KNJ, 4KNM, 4KNN, 4KP5, 4KP8

  • PubMed Abstract: 

    Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5 nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms.


  • Organizational Affiliation

    Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graičiūno 8, Vilnius LT-02241, Lithuania.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 13
A, B
263Homo sapiensMutation(s): 0 
Gene Names: CA13
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q8N1Q1 (Homo sapiens)
Explore Q8N1Q1 
Go to UniProtKB:  Q8N1Q1
PHAROS:  Q8N1Q1
GTEx:  ENSG00000185015 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8N1Q1
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
E1E Binding MOAD:  4KNM Kd: 10 (nM) from 1 assay(s)
PDBBind:  4KNM Kd: 10 (nM) from 1 assay(s)
BindingDB:  4KNM Kd: min: 8.1, max: 10 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.184 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.591α = 90
b = 58.165β = 92.16
c = 71.075γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PDB_EXTRACTdata extraction
DNAdata collection
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-06
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description