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PDBsum entry 2hl4

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protein ligands metals links
Lyase PDB id
2hl4
Jmol
Contents
Protein chain
257 a.a. *
Ligands
BO1
MBO
GOL
Metals
_ZN
_CL
Waters ×321
* Residue conservation analysis
PDB id:
2hl4
Name: Lyase
Title: Crystal structure analysis of human carbonic anhydrase ii in with a benzenesulfonamide derivative
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: sigma-aldrich co.
Resolution:
1.55Å     R-factor:   0.176     R-free:   0.198
Authors: A.Di Fiore,C.T.Supuran,J.-Y.Winum,J.-L.Montero,C.Pedone,A.Sc G.De Simone
Key ref: A.Di Fiore et al. (2007). Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-sulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties. Bioorg Med Chem Lett, 17, 1726-1731. PubMed id: 17251017 DOI: 10.1016/j.bmcl.2006.12.099
Date:
06-Jul-06     Release date:   22-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
257 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.2006.12.099 Bioorg Med Chem Lett 17:1726-1731 (2007)
PubMed id: 17251017  
 
 
Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-sulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties.
A.Di Fiore, A.Scozzafava, J.Y.Winum, J.L.Montero, C.Pedone, C.T.Supuran, G.De Simone.
 
  ABSTRACT  
 
N-(4-Sulfamoylphenyl)-alpha-d-glucopyranosylamine, a promising topical antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of its adduct with the target isoform involved in glaucoma, CA II, is reported here. The sugar sulfanilamide derivative binds to the enzyme in a totally new manner as compared to other CA-inhibitor adducts investigated earlier. The sulfonamide anchor was coordinated to the active site metal ion, and the phenylene ring of the inhibitor filled the channel leading to the active site cavity. The glycosyl moiety responsible for the high water solubility of the compound was oriented towards a hydrophilic region of the active site, where no other inhibitors were observed to be bound up to now. A network of seven hydrogen bonds with four water molecules and the amino acid residues Pro201, Pro202 and Gln92 further stabilize the enzyme-inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here. These findings are useful for the design of potent, sugar-derived enzyme inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20860527 C.Yenikaya, M.Sari, M.Bülbül, H.Ilkimen, B.Cinar, and O.Büyükgüngör (2011).
Synthesis and characterisation of two novel proton transfer compounds and their inhibition studies on carbonic anhydrase isoenzymes.
  J Enzyme Inhib Med Chem, 26, 104-114.  
21524585 Z.Xiao, R.Duan, W.Cui, Y.Zhang, S.Zhang, F.Chen, Y.Zhang, J.Liu, D.Zhang, Y.Meng, L.Wang, and H.Wang (2011).
Synthesis and evaluation of new carbonic anhydrase inhibitors.
  Bioorg Med Chem, 19, 3221-3228.  
19058143 J.Y.Winum, S.A.Poulsen, and C.T.Supuran (2009).
Therapeutic applications of glycosidic carbonic anhydrase inhibitors.
  Med Res Rev, 29, 419-435.  
19036170 F.Bootorabi, J.Jänis, J.Valjakka, S.Isoniemi, P.Vainiotalo, D.Vullo, C.T.Supuran, A.Waheed, W.S.Sly, O.Niemelä, and S.Parkkila (2008).
Modification of carbonic anhydrase II with acetaldehyde, the first metabolite of ethanol, leads to decreased enzyme activity.
  BMC Biochem, 9, 32.  
17880011 J.Y.Winum, M.Rami, A.Scozzafava, J.L.Montero, and C.Supuran (2008).
Carbonic anhydrase IX: a new druggable target for the design of antitumor agents.
  Med Res Rev, 28, 445-463.  
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.  
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.