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PDBsum entry 3b4f

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protein ligands metals links
Lyase PDB id
3b4f
Jmol
Contents
Protein chain
256 a.a. *
Ligands
TUO
Metals
_ZN
_HG
Waters ×194
* Residue conservation analysis
PDB id:
3b4f
Name: Lyase
Title: Carbonic anhydrase inhibitors. Interaction of 2- (hydrazinocarbonyl)-3-phenyl-1h-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and x-ray crystallographic studies
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.89Å     R-factor:   0.198     R-free:   0.239
Authors: O.Guzel,C.Temperini,A.Innocenti,A.Scozzafava,A.Salman, C.T.Supuran
Key ref: O.Güzel et al. (2008). Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies. Bioorg Med Chem Lett, 18, 152-158. PubMed id: 18024029 DOI: 10.1016/j.bmcl.2007.10.110
Date:
24-Oct-07     Release date:   22-Jan-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
256 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)
+ H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   11 terms 
  Biological process     angiotensin-mediated signaling pathway   21 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmcl.2007.10.110 Bioorg Med Chem Lett 18:152-158 (2008)
PubMed id: 18024029  
 
 
Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.
O.Güzel, C.Temperini, A.Innocenti, A.Scozzafava, A.Salman, C.T.Supuran.
 
  ABSTRACT  
 
2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its interaction with 12 carbonic anhydrase (CA, EC 4.2.1.1) isoforms in the search of compounds with good inhibitory activity against isozymes with medicinal chemistry applications, such as CA I, II, VA, VB, VII, IX, and XII among others. This sulfonamide is a potent inhibitor of CA I and II (K(I)s of 7.2-7.5 nM), a medium potency inhibitor of CA VII, IX, XII, and XIV, and a weak inhibitor against the other ubiquitous isoforms, making it thus a very interesting clinical candidate for situations in which a strong inhibition of CA I and II is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed many favorable interactions between the inhibitor and the enzyme which explain its strong low nanomolar affinity for this isoform but may also be exploited for the design of effective inhibitors incorporating bicyclic moieties.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19549076 F.Carta, B.Pothen, A.Maresca, M.Tiwari, V.Singh, and C.T.Supuran (2009).
Carbonic anhydrase inhibitors: inhibition of cytosolic carbonic anhydrase isozymes II and VII with simple aromatic sulfonamides and some azo dyes.
  Chem Biol Drug Des, 74, 196-202.  
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