The Mechanisms by Which Latanoprost Free Acid Inhibits Human Carbonic Anhydrase I and II(Biochemistry)
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概要
- 論文の詳細を見る
Latanoprost, a prostaglandin F2alpha analogue, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. Carbonic anhydrase (CA) inhibitors are also used to reduce ocular hypertension by decreasing aqueous humor secretion, and are given in combination with prostaglandin F2alpha analogue. It has been shown that prostaglandin F2alpha, Minprostin F_<2α>, has been shown to increase the carbonic anhydrase (CA) activity and blood pressure. However, the effects of latanoprost on CA have not been clarified. Therefore, we studied the effects of latanoprost free acid on human carbonic anhydrase (HCA) I and II using the stopped flow method. Latanoprost free acid inhibited the hydration activity of HCA I or II by a noncompetitive mechanism. The inhibition constants (K_i) of latanoprost free acid for HCA I and II were 0.22 and 2.3 mM, respectively. Therefore, latanoprost free acid is a weak inhibitor of HCA I or II. AutoDock simulation of the latanoprost free acid-HCA I or II complex showed that the carboxylic moiety of latanoprost free acid, which is located at the end of the molecule, binds to the zinc ion of the active site by stretching of the chain of latanoprost free acid through the narrow and deep active site cavity of HCA I or II. In the active site cavity of HCA I or II, one side is hydrophilic and the other is hydrophobic. AutoDock simulation results clearly showed that latanoprost free acids lie down on the hydrophobic sides of the active site cavities in HCA I and II. The noncompetitive inhibition mechanism and the binding mode of latanoprost free acid indicate that the behavior of latanoprost free acid is very similar to that of simple anions.
- 公益社団法人日本薬学会の論文
- 2008-05-01
著者
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Ikeda Hiroaki
Department Of Medical Oncology Kkr Sapporo Medical Center
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Hata Toshiyuki
Fac. Of Pharmacy And Pharmaceutical Sciences Fukuyama Univ.
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Hata Toshiyuki
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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HIROSE Junzo
Department of Food Science and Technology, Faculty of Engineering, Fukuyama University
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Kihira Kenji
Dep. Of Pharmaceutical Services Hiroshima Univ. Hospital
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Kihira Kenji
Department Of Pharmaceutical Services Hiroshima University Hospital : Division Of Clinical Pharmaceu
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Kihira Kenji
Department Of Pharmaceutical Services Hiroshima University Hospital
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ONO Yukio
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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Ono Yukio
Fac. Of Pharmacy And Pharmaceutical Sciences Fukuyama Univ.
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Ono Yukio
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Hirose Junzo
Fac. Of Pharmacy And Pharmaceutical Sciences Fukuyama Univ.
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Hirose Junzo
Department Of Applied Biological Science Faculty Of Life Science And Biotechnology Fukuyama Universi
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SUGIMOTO Ayako
Department of Pharmaceutical Services, Hiroshima University Hospital
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TSUKAMOTO Hidetoshi
Takayama Eye Clinic
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TAKEDA Chiho
Department of Applied Biological Science, Fukuyama University
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BABA Eiko
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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Takeda Chiho
Department Of Applied Biological Science Fukuyama University
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Ikeda Hiroaki
Department Of Cancer Vaccine Mie University Graduate School Of Medicine
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Hirose J
Fac. Of Pharmacy And Pharmaceutical Sciences Fukuyama Univ.
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Baba Eiko
Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Ono Yukio
Faculty of Pharmaceutical Sciences, Kyushu University
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