# Commonality of Mechanism in Glycoside Hydrolases, Nucleoside Hydrolases, and Phosphorylases: Importance of Side-Chain Conformation Preorganization

## TL;DR

This paper explores how enzymes stabilize chemical reactions by preorganizing their active sites to favor specific molecular conformations.

## Contribution

It identifies a common mechanism across diverse enzymes based on side-chain conformation preferences.

## Key findings

- Arabinofuranosidases favor the gauche,gauche conformation for electrostatic stabilization.
- Fructofuranosidases and related enzymes use the gauche,trans conformation when sterically hindered.
- The findings align with Warshel’s theory on electrostatic preorganization in enzyme catalysis.

## Abstract

A survey of the Protein Data Bank reveals that the arabinofuranosidase
class of enzymes broadly restrict their substrate side chains to
the gauche,gauche (gg) conformation
that provides maximum electrostatic stabilization to oxocarbenium
ion-like transition states and so employ the strategy reported previously
for the majority of glycoside hydrolases, transglycosidases, and glycosyltransferases
acting on pyranosyl substrates. The fructofuranosidases, ribonucleosidases,
ribonucleoside phosphorylases, and nucleoside 2′-deoxyribosyltransferases,
whose gg conformation is sterically hindered, restrict
their substrate side chains to the next most positive charge-stabilizing gauche,trans (gt) conformation. These
conclusions are supported by extensive literature studies on the mechanisms
of C–N bond cleavage by members of the nucleosidase and nucleoside
phosphorylase families and are discussed in terms of Warshel’s
concept of the electrostatic origin of the catalytic power of enzymes
and the role of preorganized active sites.