Multi-Temperature Crystallography of Polyamine Biosynthesis Enzymes Reveals Differing Active Site Conformations at RT than 100K

TL;DR

This study uses crystallography at different temperatures to better understand enzymes involved in polyamine biosynthesis, which could help in developing new drugs for cancer.

Contribution

The study reveals differing active site conformations of polyamine biosynthesis enzymes at room temperature compared to cryo-conditions.

Findings

Room temperature structures of polyamine biosynthesis enzymes differ from cryo-structures.

Dynamic enzyme conformations suggest new insights for drug design.

Abstract

The polyamine biosynthetic pathway synthesizes the polyamines putrescine, spermidine, and spermine from ornithine and S-adenosyl methionine. These polyamines are important molecules in metabolism and are associated with growth and proliferation of cells and are upregulated in many cancers. Even though this pathway has been of interest to scientists and clinicians for medical intervention, FDA approved inhibitors are unavailable, as these enzymes have proven exceptionally challenging to drug. To gather more information about the structure and dynamics of these enzymes, we have collected multi-temperature crystallography data for ornithine decarboxylase, S-adenosyl methionine decarboxylase, and spermidine synthase. Our data show dynamic enzymes where the room temperature structures differ from standard cryo- crystallography structures, improving our understanding of these enzymes and yielding insights that may be used for rational drug design.