PDBsum entry 3k2f

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Lyase PDB id
Protein chain
256 a.a. *
Waters ×120
* Residue conservation analysis
PDB id:
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
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
30-Sep-09     Release date:   17-Nov-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
260 a.a.
256 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
= 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.
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
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