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PDBsum entry 3igp

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protein ligands metals links
Lyase PDB id
3igp
Jmol
Contents
Protein chain
259 a.a. *
Ligands
DT7 ×2
GOL ×2
Metals
_ZN
Waters ×238
* Residue conservation analysis
PDB id:
3igp
Name: Lyase
Title: Structure of inhibitor binding to carbonic anhydrase ii
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:
1.65Å     R-factor:   0.161     R-free:   0.196
Authors: R.Gitto,S.Agnello,J.Brynda,P.Mader,C.T.Supuran,A.Chimirri
Key ref: R.Gitto et al. (2010). Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as potent carbonic anhydrase inhibitors: synthesis, biological evaluation, and enzyme--ligand X-ray studies. J Med Chem, 53, 2401-2408. PubMed id: 20170095 DOI: 10.1021/jm9014026
Date:
28-Jul-09     Release date:   09-Mar-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
259 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: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   10 terms 
  Biological process     angiotensin-mediated signaling pathway   20 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/jm9014026 J Med Chem 53:2401-2408 (2010)
PubMed id: 20170095  
 
 
Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as potent carbonic anhydrase inhibitors: synthesis, biological evaluation, and enzyme--ligand X-ray studies.
R.Gitto, S.Agnello, S.Ferro, L.De Luca, D.Vullo, J.Brynda, P.Mader, C.T.Supuran, A.Chimirri.
 
  ABSTRACT  
 
Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide--zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.