3SBI

Crystal structure of human carbonic anhydrase isozyme II with 4-[(2-pyrimidinylsulfanyl)acetyl]benzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.133 
  • R-Value Observed: 0.138 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Design of [(2-pyrimidinylthio)acetyl]benzenesulfonamides as inhibitors of human carbonic anhydrases.

Capkauskaite, E.Zubriene, A.Baranauskiene, L.Tamulaitiene, G.Manakova, E.Kairys, V.Grazulis, S.Tumkevicius, S.Matulis, D.

(2012) Eur J Med Chem 51: 259-270

  • DOI: https://doi.org/10.1016/j.ejmech.2012.02.050
  • Primary Citation of Related Structures:  
    3M2N, 3S8X, 3S9T, 3SAP, 3SAX, 3SBH, 3SBI

  • PubMed Abstract: 

    A series of [(2-pyrimidinylthio)acetyl]benzenesulfonamides were designed and synthesized. Their binding affinities as inhibitors of several recombinant human carbonic anhydrase (CA) isozymes were determined by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). A group of compounds containing a chlorine atom in the benzenesulfonamide ring were found to exhibit higher selectivity but lower binding affinity toward tested CAs. The crystal structures of selected compounds in complex with CA II were determined to atomic resolution. Docking studies were performed to compare the binding modes of experimentally determined crystallographic structures with computational prediction of the pyrimidine derivative binding to CA II. Several compounds bound to select CAs with single-digit nanomolar affinities and could be used as leads for inhibitor development toward a select CA isozyme.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2
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
Binding Affinity Annotations 
IDSourceBinding Affinity
E90 Binding MOAD:  3SBI Kd: 17 (nM) from 1 assay(s)
BindingDB:  3SBI Kd: min: 1.7, max: 17 (nM) from 6 assay(s)
PDBBind:  3SBI Kd: 12 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.133 
  • R-Value Observed: 0.138 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.348α = 90
b = 41.314β = 104.25
c = 72.24γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PDB_EXTRACTdata extraction
DNAdata collection

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-11
    Type: Initial release
  • Version 1.1: 2012-05-16
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Advisory, Database references
  • Version 1.3: 2023-09-13
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description