ABSTRACT
Mycobacterium tuberculosis phosphoserine phosphatase MtSerB2 is of interest as a new antituberculosis target due to its essential metabolic role in L-serine biosynthesis and effector functions in infected cells. Previous works indicated that MtSerB2 is regulated through an oligomeric transition induced by L-Ser that could serve as a basis for the design of selective allosteric inhibitors. However, the mechanism underlying this transition remains highly elusive due to the lack of experimental structural data. Here we describe a structural, biophysical, and enzymological characterisation of MtSerB2 oligomerisation in the presence and absence of L-Ser. We show that MtSerB2 coexists in dimeric, trimeric, and tetrameric forms of different activity levels interconverting through a conformationally flexible monomeric state, which is not observed in two near-identical mycobacterial orthologs. This morpheein behaviour exhibited by MtSerB2 lays the foundation for future allosteric drug discovery and provides a starting point to the understanding of its peculiar multifunctional moonlighting properties.
