A Theoretical Study on the Substrate Deacylation Mechanism of Class C beta-Lactamase 

作成者 畑, 昌之, Tanaka, Yoshikazu, Fujii, Yasuyuki, 根矢, 三郎, 星野, 忠次
作成者 (ヨミ) ハタ, マサユキ, タナカ, ヨシカズ, フジイ, ヤスユキ, ネヤ, サブロウ, ホシノ, チュウジ
作成者の別表記 Hata, Masayuki, Neya, Saburo, Hoshino, Chuji
キーワード等 beta-lactamase, deacylation, class C, quantum chemical, calculation
日本十進分類法 (NDC) 464
内容 The whole reaction of the deacylation of class C beta-lactamase was investigated by performing quantum chemical calculations under physiological conditions. In this study, the x-ray crystallographic structure of the inhibitor moxalactam-bound class C beta-lactamase (Patera et al., J. Am. Chem. Soc. 2000, 122, 10504-10512.) was utilized and moxalactam was changed into the substrate cefaclor. A model for quantum chemical calculations was constructed using an energyminimized structure of the substrate-bound enzyme obtained by molecular mechanics calculation, in which the enzyme was soaked in thousands of TIP3P water molecules. It was found that the deacylation reaction consisted of two elementary processes. The first process was formation of a tetrahedral intermediate, which was initiated by the activation of catalytic water by Tyr150, and the second process was detachment of the hydroxylated substrate from the enzyme, which associated with proton transfer from the side chain of Lys67 to Ser64Ogamma. The first process is a ratedetermining process, and the activation energy was estimated to be 30.47 kcal/mol from density functional theory calculations considering electron correlation (B3LYP/6-31G**). The side chain of Tyr150 was initially in a deprotonated state and was stably present in the active site of the acylenzymecomplex, being held by Lys67 and Lys315 cooperatively.
コンテンツの種類 雑誌掲載論文 Journal Article
DCMI資源タイプ text
ファイル形式 application/pdf
ISSN 1089-5647
NCID AA11114073
掲載誌情報 Journal of Physical Chemistry B Vol.109 no.33 page.16153-16160 (2005-08-25)
言語 英語
著者版フラグ author

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