spacer
spacer

PDBsum entry 3ibl

Go to PDB code: 
protein ligands metals links
Lyase/lyase inhibitor PDB id
3ibl
Jmol
Contents
Protein chain
258 a.a. *
Ligands
O59
HGB
Metals
_CL
_ZN
Waters ×336
* Residue conservation analysis
PDB id:
3ibl
Name: Lyase/lyase inhibitor
Title: The crystal structure of the human carbonic anhydrase ii in with an aliphatic bis-sulfamate inhibitor
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratas carbonic anhydrasE C, cac. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: erythrocytes
Resolution:
1.55Å     R-factor:   0.179     R-free:   0.200
Authors: V.Alterio,G.De Simone
Key ref: R.M.Vitale et al. (2009). Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-sulfamate adducts with isozymes II and IX as a platform for designing tight-binding, more isoform-selective inhibitors. J Med Chem, 52, 5990-5998. PubMed id: 19731956 DOI: 10.1021/jm900641r
Date:
16-Jul-09     Release date:   22-Sep-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
258 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/jm900641r J Med Chem 52:5990-5998 (2009)
PubMed id: 19731956  
 
 
Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-sulfamate adducts with isozymes II and IX as a platform for designing tight-binding, more isoform-selective inhibitors.
R.M.Vitale, V.Alterio, A.Innocenti, J.Y.Winum, S.M.Monti, G.De Simone, C.T.Supuran.
 
  ABSTRACT  
 
Two approaches were used to design inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): the tail and the ring approaches. Aliphatic sulfamates constitute a class of CA inhibitors (CAIs) that cannot be classified in either one of these categories. We report here the detailed inhibition profile of four such compounds against isoforms CAs I-XIV, the first crystallographic structures of these compounds in adduct with isoform II, and molecular modeling studies for their interaction with hCA IX. Aliphatic monosulfamates/bis-sulfamates were nanomolar inhibitors of hCAs II, IX, and XII, unlike aromatic/heterocyclic sulfonamides that promiscuously inhibit most CA isozymes with low nanomolar affinity. The bis-sulfamates incorporating 8 or 10 carbon atoms showed higher affinity for the tumor-associated hCA IX compared to hCA II, whereas the opposite was true for the monosulfamates. The explanation for their interaction with CA active site furnishes insights for obtaining compounds with increased affinity/selectivity for various isozymes.