Two classes of bacterial IMPDHs according to their quaternary structures and catalytic properties

Thomas Alexandre; Bertrand Raynal; Hélène Munier-Lehmann

doi:10.1371/journal.pone.0116578

Two classes of bacterial IMPDHs according to their quaternary structures and catalytic properties

PLoS One. 2015 Feb 23;10(2):e0116578. doi: 10.1371/journal.pone.0116578. eCollection 2015.

Authors

Thomas Alexandre¹, Bertrand Raynal, Hélène Munier-Lehmann²

Affiliations

¹ Institut Pasteur, Unité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, 28 rue du Dr Roux, F-75015, Paris, France; Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 3523, F-75015, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, F-75205, Paris, France.
² Institut Pasteur, Unité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, 28 rue du Dr Roux, F-75015, Paris, France; Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 3523, F-75015, Paris, France.

Abstract

Inosine-5'-monophosphate dehydrogenase (IMPDH) occupies a key position in purine nucleotide metabolism. In this study, we have performed the biochemical and physico-chemical characterization of eight bacterial IMPDHs, among which six were totally unexplored. This study led to a classification of bacterial IMPDHs according to the regulation of their catalytic properties and their quaternary structures. Class I IMPDHs are cooperative enzymes for IMP, which are activated by MgATP and are octameric in all tested conditions. On the other hand, class II IMPDHs behave as Michaelis-Menten enzymes for both substrates and are tetramers in their apo state or in the presence of IMP, which are shifted to octamers in the presence of NAD or MgATP. Our work provides new insights into the IMPDH functional regulation and a model for the quaternary structure modulation is proposed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacteria / metabolism
Bacterial Proteins / metabolism*
Binding Sites
Catalysis
Crystallography, X-Ray
IMP Dehydrogenase / metabolism*
Models, Molecular*
Protein Structure, Quaternary*

Substances

Bacterial Proteins
IMP Dehydrogenase

Grants and funding

This work was supported in part by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé Et de la Recherche Médicale (INSERM), and the Institut Pasteur. Thomas Alexandre was a recipient of a PhD fellowship from the Conseil Régional d’Ile-de-France and the “D.I.M. maladies infectieuses, parasitaires et nosocomiales émergentes” 2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.