His151 and His296 Are the Acid-Base Catalytic Residues of Bacillus cereus Sphingomyelinase in Sphingomyelin Hydrolysis
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概要
- 論文の詳細を見る
Bacillus cereus Sphingomyelinase belongs to the Mg^<2+>-dependent neutral sphingomyelinase, which hydrolyses sphingomyelin to phosphocholine and ceramide, and acts as an extracellular hemolysin. The triplet residues, His151-Aspl95-His296, of the enzyme are highly conserved among bacterial and mammalian Mg^<2+>-dependent neutral sphingomyelinases. The triplet residues converge on the active-site pocket of the 3D model of the enzyme. To investigate the function of these residues in the acid-base catalysis, we introduced several mutations for each residue by site-directed mutagenesis. Hemolytic and hydrolytic activities of the enzyme, abolished by the mutations at Asp195 and His296, revealed that these residues are critical for the catalytic function. The effect of the divalent metal cations on the pH dependency of the hydrolytic activities indicates that His296 corresponds to the most acidic ionizable group as a general base. The mutagenesis at His151 was also deleterious; however, the H151A and H151Q mutant enzymes partially retained their activities. The H151A mutation affected the most basic ionizable group, suggesting that His151 may act as a general acid in catalysis. By the structural basis of the 3D model, Asp195 must maintain not only the appropriate spatial arrangement but also pK_as of His151 and His296. Taking into consideration all of these, we proposed the acid-base catalytic mechanism of B. cereus sphingomyelinase.
- 社団法人日本薬学会の論文
- 2003-07-01
著者
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IMAGAWA Masayoshi
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University
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藤井 忍
大阪薬大・生化
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池田 潔
School Of Pharmaceutical Sciences University Of Shizuoka
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池田 潔
Tanabe Seiyaku Co. Ltd. Saitama Jpn
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TSUKAMOTO Kikuo
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University
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OBAMA Takashi
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University
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FUJII Shinobu
Osaka University of Pharmaceutical Sciences
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IKEZAWA Hiroh
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University
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IKEDA Kiyoshi
Osaka University of Pharmaceutical Sciences
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Ikezawa H
Department Of Molecular Biology Graduate School Of Pharmaceutical Sciences Nagoya City University
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Ikeda Kiyoshi
Department Of Biochemistry Osaka University Of Pharmaceutical Sciences
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Obama Takashi
Department Of Molecular Biology Graduate School Of Pharmaceutical Sciences Nagoya City University
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Tsukamoto K
Department Of Molecular Biology Graduate School Of Pharmaceutical Sciences Nagoya City University
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池田 かおり
Developmental Research Laboratories Shionogi & Co. Ltd.
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Ikeda Kaori
Developmental Research Laboratories Shionogi & Co. Ltd.
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Imagawa Masayoshi
Department Of Molecular Biology Graduate School Of Pharmaceutical Sciences Nagoya City University
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Imagawa Masayoshi
Department Of Environmental Biochemistry Faculty Of Pharmaceutical Sciences Osaka University
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