Timolol activates the enzyme activities of human carbonic anhydrase I and II

Biological & Pharmaceutical Bulletin
Ayako SugimotoYukio Ono

Abstract

Timolol, a beta-blocker, has been shown to be an effective ocular hypotensive agent when used alone or with carbonic anhydrase inhibitor on ocular hypertensive or open angle glaucoma patients. The effect of timolol hemihydrate on the CO(2) hydration activities of human carbonic anhydrase (HCA) I and II and their reaction mechanisms were investigated. Timolol activates the enzyme activities of HCA I and HCA II. In HCA I and II, the enzyme kinetic results clearly showed that timolol increases the value of V(max) but does not influence the value of K(m). The enzyme kinetic method showed that timolol noncompetitively activates HCA I and II activities through the formation of a ternary complex consisting of the enzyme, the substrate, and timolol. These results indicate that timolol binds apart from the narrow cavity of the active site. AutoDocking results showed that timolol binds at the entrance of the active site cavity in a region where the proton shuttle residue, His 64, of HCA I or II, is placed. The enzyme kinetic and AutoDocking results showed that timolol might weakly bind near the proton shuttle residue, His 64, to accelerate the proton transfer rate from His 64 to the buffer components. It is known that efficient activator...Continue Reading

References

Apr 1, 1986·Archives of Internal Medicine·J A BannonJ J Schrogie
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·V KumarP Sathyamurthi
Apr 29, 2005·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Hidetoshi TsukamotoHiromu K Mishima
Jan 21, 2006·International Journal of Pharmaceutics·Tommy TarvainenKristiina Järvinen
Jul 28, 2006·Bioorganic & Medicinal Chemistry Letters·Claudia TemperiniClaudiu T Supuran
Nov 21, 2007·Drugs & Aging·Albert S KhouriRobert D Fechtner
Nov 27, 2007·Expert Opinion on Pharmacotherapy·Jess T Whitson
May 3, 2008·Biological & Pharmaceutical Bulletin·Ayako SugimotoYukio Ono
Jul 11, 2008·Nature·Antonio Damasio, Kaspar Meyer

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Citations

Sep 4, 2018·Expert Opinion on Therapeutic Patents·Claudiu T Supuran
Feb 27, 2018·Future Medicinal Chemistry·Claudiu T Supuran
Nov 5, 2014·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Junzo Hirose
Oct 27, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClaudiu T Supuran

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