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PDBsum entry 4ht2

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protein ligands metals Protein-protein interface(s) links
Lyase/lyase inhibitor PDB id
4ht2
Jmol
Contents
Protein chain
261 a.a.
Ligands
V50 ×4
PEG ×3
EDO ×12
Metals
_ZN ×4
Waters ×1504
PDB id:
4ht2
Name: Lyase/lyase inhibitor
Title: Crystal structure of human carbonic anhydrase isozyme xii wi inhibitor.
Structure: Carbonic anhydrase 12. Chain: a, b, c, d. Fragment: human carbonic anhydrase xii. Synonym: carbonate dehydratase xii, carbonic anhydrase xii, tumor antigen hom-rcc-3.1.3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca12. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.45Å     R-factor:   0.154     R-free:   0.188
Authors: A.Smirnov,E.Manakova,S.Grazulis
Key ref: V.Dudutienė et al. (2013). 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII. Bioorg Med Chem, 21, 2093-2106. PubMed id: 23394791 DOI: 10.1016/j.bmc.2013.01.008
Date:
31-Oct-12     Release date:   10-Apr-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O43570  (CAH12_HUMAN) -  Carbonic anhydrase 12
Seq:
Struc:
354 a.a.
261 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.1  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
H(2)CO(3)
=
CO(2)
Bound ligand (Het Group name = EDO)
matches with 40.00% similarity
+ H(2)O
      Cofactor: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     one-carbon metabolic process   1 term 
  Biochemical function     carbonate dehydratase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmc.2013.01.008 Bioorg Med Chem 21:2093-2106 (2013)
PubMed id: 23394791  
 
 
4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII.
V.Dudutienė, A.Zubrienė, A.Smirnov, J.Gylytė, D.Timm, E.Manakova, S.Gražulis, D.Matulis.
 
  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.