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PDBsum entry 3f4x

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protein ligands metals links
Lyase PDB id
3f4x
Jmol
Contents
Protein chain
256 a.a. *
Ligands
KLT
Metals
_ZN
_HG
Waters ×190
* Residue conservation analysis
PDB id:
3f4x
Name: Lyase
Title: Carbonic anhydrase inhibitors. Comparison of chlorthalidone and indapamide x-ray crystal structures in adducts with isozyme ii: when three water molecules make the difference
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratase ii, carbonic anhydrasE C, cac. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.90Å     R-factor:   0.202     R-free:   0.252
Authors: C.Temperini,A.Cecchi,A.Scozzafava,C.T.Supuran
Key ref: C.Temperini et al. (2009). Carbonic anhydrase inhibitors. Comparison of chlorthalidone and indapamide X-ray crystal structures in adducts with isozyme II: when three water molecules and the keto-enol tautomerism make the difference. J Med Chem, 52, 322-328. PubMed id: 19115843 DOI: 10.1021/jm801386n
Date:
03-Nov-08     Release date:   17-Mar-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   21 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/jm801386n J Med Chem 52:322-328 (2009)
PubMed id: 19115843  
 
 
Carbonic anhydrase inhibitors. Comparison of chlorthalidone and indapamide X-ray crystal structures in adducts with isozyme II: when three water molecules and the keto-enol tautomerism make the difference.
C.Temperini, A.Cecchi, A.Scozzafava, C.T.Supuran.
 
  ABSTRACT  
 
Thiazide diuretics inhibit all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a different profile as compared to classical inhibitors. Acting as moderate-weak inhibitors of CA II and CA I, chlorthalidone and indapamide considerably inhibit other isozymes among the 16 CAs present in vertebrates. These compounds show a different behavior against CAs I and II, with chlorthalidone being 18.3 times more potent against CA II and 150 times more potent against CA I, as compared to indapamide. In the X-ray crystal structures of the CA II-chlorthalidone adduct three active site water molecules interacting with the inhibitor scaffold were observed that lack in the corresponding indapamide adduct. Chlorthalidone bound within the active site is in an enolic tautomeric form, with the OH moiety participating in two strong hydrogen bonds with Asn67 and a water molecule. This binding mode may be exploited for designing better CA II inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21470859 M.Rami, A.Maresca, F.Z.Smaine, J.L.Montero, A.Scozzafava, J.Y.Winum, and C.T.Supuran (2011).
Sulfonamides incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII.
  Bioorg Med Chem Lett, 21, 2975-2979.  
19657719 B.K.Sharma, P.Pilania, K.Sarbhai, P.Singh, and Y.S.Prabhakar (2010).
Chemometric descriptors in modeling the carbonic anhydrase inhibition activity of sulfonamide and sulfamate derivatives.
  Mol Divers, 14, 371-384.  
20354892 J.R.Greenwood, D.Calkins, A.P.Sullivan, and J.C.Shelley (2010).
Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution.
  J Comput Aided Mol Des, 24, 591-604.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.