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PDBsum entry 3ffp

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protein ligands metals links
Lyase PDB id
3ffp
Jmol
Contents
Protein chain
256 a.a. *
Ligands
LC1
BEZ
Metals
_ZN
_HG
Waters ×193
* Residue conservation analysis
PDB id:
3ffp
Name: Lyase
Title: X ray structure of the complex between carbonic anhydrase ii and lc inhibitors
Structure: Carbonic anhydrase 2. Chain: x. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratase ii, carbonic anhydrasE C, cac. Engineered: yes
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Other_details: this sequence occurs naturally in humans.
Resolution:
1.81Å     R-factor:   0.189     R-free:   0.240
Authors: C.Temperini,L.Crocetti,A.Scozzafava,C.T.Supuran
Key ref: L.Crocetti et al. (2009). A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases. Bioorg Med Chem Lett, 19, 1371-1375. PubMed id: 19186056 DOI: 10.1016/j.bmcl.2009.01.038
Date:
04-Dec-08     Release date:   18-Aug-09    
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   22 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmcl.2009.01.038 Bioorg Med Chem Lett 19:1371-1375 (2009)
PubMed id: 19186056  
 
 
A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases.
L.Crocetti, A.Maresca, C.Temperini, R.A.Hall, A.Scozzafava, F.A.Mühlschlegel, C.T.Supuran.
 
  ABSTRACT  
 
A sulfonamide derivative of the antihelmintic drug thiabendazole was prepared and investigated for inhibition of the zinc enzyme carbonic anhydrase CA (EC 4.2.1.1). Mammalian isoforms CA I-XIV and the nematode enzyme of Caenorhabditis elegans CAH-4b were included in this study. Thiabendazole-5-sulfonamide was a very effective inhibitor of CAH-4b and CA IX (K(I)s of 6.4-9.5nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with K(I)s in the range of 17.8-73.2nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19648295 J.Giacomotto, C.Pertl, C.Borrel, M.C.Walter, S.Bulst, B.Johnsen, D.L.Baillie, H.Lochmüller, C.Thirion, and L.Ségalat (2009).
Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy.
  Hum Mol Genet, 18, 4089-4101.  
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