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PDBsum entry 2o4z

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protein ligands metals links
Lyase PDB id
2o4z
Jmol
Contents
Protein chain
256 a.a. *
Ligands
HSW
Metals
_ZN
_HG
Waters ×162
* Residue conservation analysis
PDB id:
2o4z
Name: Lyase
Title: Crystal structure of the carbonic anhydrase ii complexed with hydroxysulfamide inhibitor
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
2.10Å     R-factor:   0.210     R-free:   0.266
Authors: C.Temperini,J.Y.Winum,J.L.Montero,A.Scozzafava,C.T.Supuran
Key ref: C.Temperini et al. (2007). Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors. Bioorg Med Chem Lett, 17, 2795-2801. PubMed id: 17346964 DOI: 10.1016/j.bmcl.2007.02.068
Date:
05-Dec-06     Release date:   15-May-07    
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: 10.1016/j.bmcl.2007.02.068 Bioorg Med Chem Lett 17:2795-2801 (2007)
PubMed id: 17346964  
 
 
Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors.
C.Temperini, J.Y.Winum, J.L.Montero, A.Scozzafava, C.T.Supuran.
 
  ABSTRACT  
 
N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N-hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
18437247 K.Devanathan, J.A.Bell, P.C.Wilkins, H.K.Jacobs, and A.S.Gopalan (2007).
Synthetic methodology for the preparation of N-hydroxysulfamides.
  Tetrahedron Lett, 48, 8029-8033.  
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