2014年4月
Nylon-Oligomer Hydrolase Promoting Cleavage Reactions in Unnatural Amide Compounds
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
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- 巻
- 5
- 号
- 7
- 開始ページ
- 1210
- 終了ページ
- 1216
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/jz500323y
- 出版者・発行元
- AMER CHEMICAL SOC
The active site of 6-aminohexanoate-dimer hydrolase, a nylon-6 byproduct-degrading enzyme with a beta-lactamase fold, possesses a Ser112/Lys115/Tyr215 catalytic triad similar to the one of penicillin-recognizing family of serine-reactive hydrolases but includes a unique Tyr170 residue. By using a reactive quantum mechanics/molecular mechanics (QM/MM) approach, we work out its catalytic mechanism and related functional/structural specificities. At variance with other peptidases, we show that the involvement of Tyr170 in the enzyme-substrate interactions is responsible for a structural variation in the substrate-binding state. The acylation via a tetrahedral intermediate is the rate-limiting step, with a free-energy barrier of similar to 21 kcal/mol, driven by the catalytic triad Ser112, Lys115, and Tyr215, acting as a nucleophile, general base, and general acid, respectively. The functional interaction of Tyr170 with this triad leads to an efficient disruption of the tetrahedral intermediate, promoting a conformational change of the substrate favorable for proton donation from the general acid.
- リンク情報
- ID情報
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- DOI : 10.1021/jz500323y
- ISSN : 1948-7185
- PubMed ID : 26274473
- Web of Science ID : WOS:000333947700027