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

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Dimitriou PS, Denesyuk AI, Nakayama T, Johnson MS, Denessiouk K.
Publisher: Wiley
Publication year: 2019
Journal: Protein Science
Volume number: 28
Issue number: 2
Start page: 344
End page: 364


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.

Last updated on 2019-24-04 at 02:11