TY - JOUR
T1 - A morpheein equilibrium regulates catalysis in phosphoserine phosphatase SerB2 from Mycobacterium tuberculosis
AU - Pierson, Elise
AU - De Pol, Florian
AU - Fillet, Marianne
AU - Wouters, Johan
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/10/10
Y1 - 2023/10/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85173716050&partnerID=8YFLogxK
U2 - 10.1038/s42003-023-05402-z
DO - 10.1038/s42003-023-05402-z
M3 - Article
C2 - 37817000
AN - SCOPUS:85173716050
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1024
ER -