Serine/threonine protein phosphatases are central mediators of phosphorylation-dependent signals in eukaryotes and a variety of pathogenic bacteria. Here, we report the crystal structure of the intracellular catalytic domain of Mycobacterium tuberculosis PstPpp, a membrane-anchored phosphatase in the PP2C family. Despite sharing the fold and two-metal center of human PP2Cα, the PstPpp catalytic domain binds a third Mn2+ in a site created by a large shift in a previously unrecognized flap subdomain adjacent to the active site. Mutations in this site selectively increased the Michaelis constant for Mn2+ in the reaction of a noncognate, small-molecule substrate, p-nitrophenyl phosphate. The PstP/Ppp structure reveals core functional motifs that advance the framework for understanding the mechanisms of substrate recognition, catalysis, and regulation of PP2C phosphatases.
Pullen, K. E., Ng, H. L., Sung, P. Y., Good, M. C., Smith, S. M., & Alber, T. (2004). An alternate conformation and a third metal in PstP/Ppp, the M. tuberculosis PP2C-family Ser/Thr protein phosphatase. Structure, 12(11), 1947–1954. https://doi.org/10.1016/j.str.2004.09.008