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PDBsum entry 2hoc

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protein ligands metals links
Lyase PDB id
2hoc
Jmol
Contents
Protein chain
258 a.a. *
Ligands
1CN ×2
MBO
GOL
Metals
_ZN
Waters ×161
* Residue conservation analysis
PDB id:
2hoc
Name: Lyase
Title: Crystal structure of the human carbonic anhydrase ii in comp the 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-th 2-sulfonamide inhibitor
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, c carbonic anhydrasE C. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: human erythrocytes
Resolution:
2.10Å     R-factor:   0.184     R-free:   0.223
Authors: V.Menchise,A.Di Fiore,G.De Simone
Key ref: V.Menchise et al. (2006). Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II. Bioorg Med Chem Lett, 16, 6204-6208. PubMed id: 17000110 DOI: 10.1016/j.bmcl.2006.09.022
Date:
14-Jul-06     Release date:   10-Oct-06    
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: 10.1016/j.bmcl.2006.09.022 Bioorg Med Chem Lett 16:6204-6208 (2006)
PubMed id: 17000110  
 
 
Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II.
V.Menchise, G.De Simone, A.Di Fiore, A.Scozzafava, C.T.Supuran.
 
  ABSTRACT  
 
The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the two compounds binds in the canonic manner to the zinc ion and interacts with Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor was positioned in the hydrophobic part of the binding pocket, at van der Waals distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These structures may help in the design of better inhibitors of these widespread zinc-containing enzymes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21354674 J.Liu, D.Obando, V.Liao, T.Lifa, and R.Codd (2011).
The many faces of the adamantyl group in drug design.
  Eur J Med Chem, 46, 1949-1963.  
20157916 H.Park, S.Kim, Y.E.Kim, and S.J.Lim (2010).
A structure-based virtual screening approach toward the discovery of histone deacetylase inhibitors: identification of promising zinc-chelating groups.
  ChemMedChem, 5, 591-597.  
18335973 V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
  Chem Rev, 108, 946.  
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