Insight into the role of the Bateman domain at the molecular and physiological levels through engineered IMP dehydrogenases

Inosine 5' -monophosphate (IMP) dehydrogenase (IMPDH) is an ubiquitous enzyme that catalyzes the NAD(+)-dependent oxidation of inosine 5' monophosphate into xanthosine 5'-monophosphate. This enzyme is formed of two distinct domains, a core domain where the catalytic reaction occurs, and a less-conserved Bateman domain. Our previous studies gave rise to the classification of bacterial IMPDHs into two classes, according to their oligomeric and kinetic properties. MgATP is a common effector but cause to different effects when it binds within the Bateman domain: it is either an allosteric activator for Class I IMPDHs or a modulator of the oligomeric state for Class II IMPDHs. To get insight into the role of the Bateman domain in the dissimilar properties of the two classes, deleted variants of the Bateman domain and chimeras issued from the interchange of the Bateman domain between the three selected IMPDHs have been generated and characterized using an integrative structural biology approach. Biochemical, biophysical, structural, and physiological studies of these variants unveil the Bateman domain as being the carrier of the molecular behaviors of both classes.

Automated summary

Inosine 5' -monophosphate dehydrogenase (IMPDH) is an enzyme that oxidizes inosine 5' monophosphate into xanthosine 5'-monophosphate. It consists of a core domain for catalytic reaction and a less-conserved Bateman domain. Two classes of bacterial IMPDHs have been classified based on their oligomeric and kinetic properties, with MgATP acting as an activator for Class I and a modulator of oligomeric state for Class II. Analysis of deleted variants and chimeras revealed the Bateman domain's role in the different properties of the two classes.