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Article Dans Une Revue Journal of Physical Chemistry Letters Année : 2014

Nylon-Oligomer Hydrolase Promoting Cleavage Reactions in Unnatural Amide Compounds

Résumé

The active site of 6-aminohexanoate-dimer hydrolase, a nylon-6 byproduct-degrading enzyme with a β-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 ∼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.
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Dates et versions

hal-02991778 , version 1 (04-12-2020)

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Katsumasa Kamiya, Takeshi Baba, Mauro Boero, Toru Matsui, Seiji Negoro, et al.. Nylon-Oligomer Hydrolase Promoting Cleavage Reactions in Unnatural Amide Compounds. Journal of Physical Chemistry Letters, 2014, 5 (7), pp.1210-1216. ⟨10.1021/jz500323y⟩. ⟨hal-02991778⟩
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