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Structure. 2004 Nov;12(11):1947-54.

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

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1
Department of Molecular and Cell Biology, 339 Hildebrand Hall #3206, University of California, Berkeley, Berkeley, CA 94720, USA.

Abstract

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 Mn(2+) 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 Mn(2+) 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.

PMID:
15530359
DOI:
10.1016/j.str.2004.09.008
[Indexed for MEDLINE]
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