4KNN

Crystal structure of human carbonic anhydrase isozyme XIII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.169 

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This is version 1.2 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 13A [auth B],
B [auth A]
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
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
E1F
Query on E1F

Download Ideal Coordinates CCD File 
D [auth B],
L [auth A]
2-chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide
C12 H10 Cl N3 O3 S2
ZQEDEEFNLDNUEW-UHFFFAOYSA-N
CIT
Query on CIT

Download Ideal Coordinates CCD File 
E [auth B],
M [auth A]
CITRIC ACID
C6 H8 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
N [auth A]DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
ZN
Query on ZN

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

Download Ideal Coordinates CCD File 
F [auth B],
G [auth B],
O [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
H [auth B],
I [auth B],
J [auth B]
ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
E1F BindingDB:  4KNN Kd: min: 1, max: 17 (nM) from 5 assay(s)
PDBBind:  4KNN Kd: 16.7 (nM) from 1 assay(s)
Binding MOAD:  4KNN Kd: 16.7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.169 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.182α = 90
b = 57.47β = 90
c = 159.467γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
SCALAdata scaling
PDB_EXTRACTdata extraction
DNAdata collection
XDSdata reduction
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: 2018-05-16
    Changes: Data collection, Refinement description
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description