An alternate conformation and a third metal in PstP/Ppp, the M-tuberculosis PP2C-family Ser/Thr protein phosphatase

作者：Pullen KE; Ng HL; Sung PY; Good MC; Smith SM; Alber T^*

来源：Structure, 2004, 12(11): 1947-1954.

DOI：10.1016/j.str.2004.09.008

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 PP2Calpha, 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 non-cognate, 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.

• 出版日期2004-11