2HNC

Crystal structure of the human carbonic anhydrase II in complex with the 5-amino-1,3,4-thiadiazole-2-sulfonamide inhibitor.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.194 

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This is version 1.3 of the entry. See complete history


Literature

Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II.

Menchise, V.De Simone, G.Di Fiore, A.Scozzafava, A.Supuran, C.T.

(2006) Bioorg Med Chem Lett 16: 6204-6208

  • DOI: https://doi.org/10.1016/j.bmcl.2006.09.022
  • Primary Citation of Related Structures:  
    2HNC, 2HOC

  • PubMed Abstract: 

    The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the two compounds binds in the canonic manner to the zinc ion and interacts with Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor was positioned in the hydrophobic part of the binding pocket, at van der Waals distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These structures may help in the design of better inhibitors of these widespread zinc-containing enzymes.


  • Organizational Affiliation

    Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Naples, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2259Homo sapiensMutation(s): 0 
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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
1SA Binding MOAD:  2HNC Ki: 60 (nM) from 1 assay(s)
BindingDB:  2HNC Ki: min: 60, max: 6.00e+4 (nM) from 4 assay(s)
IC50: min: 2750, max: 7400 (nM) from 6 assay(s)
PDBBind:  2HNC Ki: 60 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.194 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.11α = 90
b = 41.31β = 104.35
c = 71.89γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-12-19
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description