Distinctive structural motifs co-ordinate the catalytic nucleophile and the residues of the oxyanion hole in the alpha/beta-hydrolase fold enzymes

Polytimi Dimitriou, Alexandre Denesyuk, T Nakayama, Mark S Johnson, Konstantin Denessiouk

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)
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Abstract

The alpha/beta-hydrolases (ABH) are among the largest structural families of proteins that are found in nature. Although they vary in their sequence and function, the ABH enzymes use a similar acid-base-nucleophile catalytic mechanism to catalyze reactions on different substrates. Because ABH enzymes are biocatalysts with a wide range of potential applications, protein engineering has taken advantage of their catalytic versatility to develop enzymes with industrial applications. This study is a comprehensive analysis of 40 ABH enzyme families focusing on two identified substructures: the nucleophile zone and the oxyanion zone, which co-ordinate the catalytic nucleophile and the residues of the oxyanion hole, and independently reported as critical for the enzymatic activity. We also frequently observed an aromatic cluster near the nucleophile and oxyanion zones, and opposite the ligand-binding site. The nucleophile zone, the oxyanion zone and the residue cluster enriched in aromatic side chains comprise a three-dimensional structural organization that shapes the active site of ABH enzymes and plays an important role in the enzymatic function by structurally stabilizing the catalytic nucleophile and the residues of the oxyanion hole. The structural data support the notion that the aromatic cluster can participate in co-ordination of the catalytic histidine loop, and properly place the catalytic histidine next to the catalytic nucleophile.

Original languageUndefined/Unknown
Pages (from-to)344–364
JournalProtein Science
Volume28
Issue number2
DOIs
Publication statusPublished - 2019
MoE publication typeA1 Journal article-refereed

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