advertisement
Abstract #25386 Published in IGR 12-1
Inhibition and activation of carbonic anhydrase I and II activities by effective ocular hypotensive agents (timolol and latanoprost)
Hirose J; Hata T; Ono YJournal of Biological Inorganic Chemistry 2009; 14: S194-S195
Several types of agents such as beta-blockers (e.g. timolol), prostaglandins (e.g. latanoprost) and carbonic anhydrase (CA) inhibitors are clinically used in the treatment of glaucoma. CA inhibitors are often used as the adjunctive agent to anti-glaucoma agents such as timolol and latanoprost. The effects of timolol and latanoprost on CA activities were investigated by the enzyme kinetics. In our results, latanoprost was a noncompetitive inhibitor (Ki = 0.24 mM), but timolol noncompetitively activated CA activity (KA > 3 mM). AutoDock simulations of timolol and latanoprost with CA clearly showed that latanoprost binds to the zinc ion, which is located at the bottom of the narrow cavity of CA, by the long chain of latanoprost (Fig. 1a) and that timolol binds to the entrance of the active site cavity of CA in a region where the proton shuttle residue, His 64, is placed (Fig. 1b). The results of AutoDock simulations strongly substantiate the observations obtained by the enzyme kinetics.
J. Hirose. Faculty of Pharmacy and Pharmceutical Science, Fukuyama University, FukuyamaJapan. hirose@fupharm.fukuyama-u.ac.jp
Classification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
11.4 Prostaglandins (Part of: 11 Medical treatment)
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
