title: Two classes of bacterial IMPDHs according to their quaternary structures and catalytic properties.
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.
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alexandre
authors.forename: Bertrand
authors.initials: B
authors.lastname: Raynal
authors.affiliation: Institut Pasteur, Proteopole, Plateforme de biophysique des macromolecules et de leurs interactions, 25 rue du Dr Roux, F-75015, Paris, France; Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 3528, F-75015, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Rayna
authors.affiliation: 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.
authors.forename: Hélène
authors.initials: H
authors.lastname: Munier-Lehmann
mesh_terms: D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D007168:IMP Dehydrogenase / Q000378:metabolism*; D008958:Models, Molecular; D020836:Protein Structure, Quaternary
chemical_list: D001426:Bacterial Proteins; D007168:IMP Dehydrogenase