4HU1

Crystal structure of human carbonic anhydrase isozyme XIII with the inhibitor.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.175 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII.

Dudutiene, V.Zubriene, A.Smirnov, A.Gylyte, J.Timm, D.Manakova, E.Grazulis, S.Matulis, D.

(2013) Bioorg Med Chem 21: 2093-2106

  • DOI: https://doi.org/10.1016/j.bmc.2013.01.008
  • Primary Citation of Related Structures:  
    4HT0, 4HT2, 4HU1

  • PubMed Abstract: 

    A series of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides were synthesized and their binding potencies as inhibitors of recombinant human carbonic anhydrase isozymes I, II, VII, XII, and XIII were determined by the thermal shift assay, isothermal titration calorimetry, and stop-flow CO2 hydration assay. All fluorinated benzenesulfonamides exhibited nanomolar binding potency toward tested CAs and fluorinated benzenesulfonamides posessed higher binding potency than non-fluorinated compounds. The crystal structures of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide in complex with CA II and CA XII, and 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide in complex with CA XIII were determined. The observed dissociation constants for several fluorinated compounds reached subnanomolar range for CA I isozyme. The affinity and the selectivity of the compounds towards tested isozymes are presented.


  • Organizational Affiliation

    Department of Biothermodynamics and Drug Design,Vilnius University Institute of Biotechnology, 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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
V13
Query on V13

Download Ideal Coordinates CCD File 
D [auth B],
H [auth A]
2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide
C8 H7 F4 N O5 S2
WZGGLNWNBUCLIP-UHFFFAOYSA-N
PEG
Query on PEG

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

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

Download Ideal Coordinates CCD File 
E [auth B]
F [auth B]
J [auth A]
K [auth A]
L [auth A]
E [auth B],
F [auth B],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
V13 BindingDB:  4HU1 Kd: min: 29, max: 74 (nM) from 3 assay(s)
Binding MOAD:  4HU1 Kd: 29 (nM) from 1 assay(s)
PDBBind:  4HU1 Kd: 29 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.27α = 90
b = 57.386β = 90
c = 159.552γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PDB_EXTRACTdata extraction
MAR345dtbdata 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: 2013-04-10
    Type: Initial release
  • Version 1.1: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description