Nylon-Oligomer Hydrolase Promoting Cleavage Reactions in Unnatural Amide Compounds
Year: 2014
Type: article
Abstract: 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.
DOI: 10.1021/jz500323y
Institutions: Kanagawa Institute of Technology, The University of Osaka, Centre National de la Recherche Scientifique, Institut de Physique et Chimie des Matériaux de Strasbourg, Université de Strasbourg, RIKEN, RIKEN Center for Computational Science, University of Hyogo, Japan Science and Technology Agency
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: Molecular design of nylon oligomer degradation enzyme and its application to bioproduction, Molecular design of nylon hydrolase and industrial application of the enzyme, 分子動力学法に基づくタンパク質反応場の理解とタンパク質デザイン, Biodegradation of nylon and its recycle, G7965730075, Quantum Mechanical Studies of Proton Affinity of Amino Acid Residues in Protein Environments
OpenAlex ID: W2018454553