Timolol activates the enzyme activities of human carbonic anhydrase 1 and 2
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- Sugimoto Ayako
- Department of Pharmaceutical Services, Hiroshima University Hospital
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- Ikeda Hiroaki
- Department of Pharmaceutical Services, Hiroshima University Hospital
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- Tsukamoto Hidetoshi
- Takayama Eye Clinic
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- Kihira Kenji
- Department of Pharmaceutical Services, Hiroshima University Hospital
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- Ishioka Manabu
- Department of Applied Biological Science, Fukuyama University
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- Hirose Junzo
- Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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- Hata Toshiyuki
- Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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- Fujioka Haruto
- Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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- Ono Yukio
- Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
書誌事項
- タイトル別名
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- Timolol Activates the Enzyme Activities of Human Carbonic Anhydrase I and II
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抄録
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 CO2 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 Vmax but does not influence the value of Km. 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 activators of carbonic anhydrase possess a bulky aromatic/heterocyclic moiety and a primary/secondary amino group in their molecular structure. Timolol has a heterocyclic moiety and a secondary amino group, which are typical structures in efficient activators of carbonic anhydrase.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 33 (2), 301-306, 2010
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204625506944
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- NII論文ID
- 130000156641
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3c%2FmvFeitQ%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 10536990
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- PubMed
- 20118557
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可