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PDBsum entry 3k2f

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protein ligands metals links
Lyase PDB id
3k2f
Jmol
Contents
Protein chain
256 a.a. *
Ligands
NKX
Metals
_ZN
_HG
Waters ×120
* Residue conservation analysis
PDB id:
3k2f
Name: Lyase
Title: Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C, cac. Engineered: yes
Source: Synthetic: yes. Other_details: this sequence occurs naturally in humans
Resolution:
1.98Å     R-factor:   0.220     R-free:   0.272
Authors: C.Temperini,A.Cecchi
Key ref: R.M.Steele et al. (2009). Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma. Bioorg Med Chem Lett, 19, 6565-6570. PubMed id: 19854054 DOI: 10.1016/j.bmcl.2009.10.036
Date:
30-Sep-09     Release date:   17-Nov-09    
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.2009.10.036 Bioorg Med Chem Lett 19:6565-6570 (2009)
PubMed id: 19854054  
 
 
Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma.
R.M.Steele, F.Benedini, S.Biondi, V.Borghi, L.Carzaniga, F.Impagnatiello, D.Miglietta, W.K.Chong, R.Rajapakse, A.Cecchi, C.Temperini, C.T.Supuran.
 
  ABSTRACT  
 
Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21549597 F.Mincione, F.Benedini, S.Biondi, A.Cecchi, C.Temperini, G.Formicola, I.Pacileo, A.Scozzafava, E.Masini, and C.T.Supuran (2011).
Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action.
  Bioorg Med Chem Lett, 21, 3216-3221.
PDB code: 3ni5
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. Where a reference describes a PDB structure, the PDB code is shown on the right.