# Allosteric properties of mammalian ALOX15 orthologs

## TL;DR

This paper reviews the allosteric properties of mammalian ALOX15 enzymes and evaluates two competing hypotheses about their molecular mechanism.

## Contribution

The paper critically evaluates two hypotheses regarding the allosteric mechanism of mammalian ALOX15 orthologs.

## Key findings

- Mammalian ALOX15 orthologs are allosteric enzymes with distinct biological functions.
- Two hypotheses about the allosteric mechanism of ALOX15 are compared in the paper.

## Abstract

Lipoxygenases (arachidonic acid lipoxygenase [ALOX]) are non-heme iron–containing dioxygenases that catalyze the oxygenation of polyenoic fatty acid–containing lipids to their corresponding hydroperoxy derivatives. These enzymes are widely distributed in highly developed plants and animals. In bacteria, they rarely occur, but they have not been detected in archaea and viruses. The human genome involves six functional ALOX genes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, and ALOX5) encoding for six different isoenzymes. The mouse genome carries an orthologous gene for each human ALOX gene, but in addition, an Aloxe12 gene has been identified in this species. The application of isoenzyme-specific loss-of-function strategies suggested that the coding multiplicity may not be interpreted as a sign of functional redundancy. In fact, the different isoenzymes apparently fulfill different biological functions. Mammalian ALOX15 orthologs are allosteric enzymes, but the molecular basis for their allosteric properties remains controversial. In fact, two alternative hypotheses (the presence of allosteric binding sites at enzyme monomers versus ALOX15 dimers consist of an allosteric and a catalytic monomer) have been introduced, and this review is aimed at critically evaluating the pros and cons of these two mechanistic scenarios.