1wao

From Proteopedia

Revision as of 17:42, 12 November 2007

PP5 STRUCTURE

Overview

Protein phosphatase 5 (Ppp5) is a serine/threonine protein phosphatase, comprising a regulatory tetratricopeptide repeat (TPR) domain N-terminal, to its phosphatase domain. Ppp5 functions in signalling pathways that, control cellular responses to stress, glucocorticoids and DNA damage. Its, phosphatase activity is suppressed by an autoinhibited conformation, maintained by the TPR domain and a C-terminal subdomain. By interacting, with the TPR domain, heat shock protein 90 (Hsp90) and fatty acids, including arachidonic acid stimulate phosphatase activity. Here, we, describe the structure of the autoinhibited state of Ppp5, revealing, mechanisms of TPR-mediated phosphatase inhibition and Hsp90- and, arachidonic acid-induced stimulation of phosphatase activity. The TPR, domain engages with the catalytic channel of the phosphatase domain, restricting access to the catalytic site. This autoinhibited conformation, of Ppp5 is stabilised by the C-terminal alphaJ helix that contacts a, region of the Hsp90-binding groove on the TPR domain. Hsp90 activates Ppp5, by disrupting TPR-phosphatase domain interactions, permitting substrate, access to the constitutively active phosphatase domain, whereas, arachidonic acid prompts an alternate conformation of the TPR domain, destabilising the TPR-phosphatase domain interface.

About this Structure

1WAO is a Single protein structure of sequence from Homo sapiens with MN as ligand. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Molecular basis for TPR domain-mediated regulation of protein phosphatase 5., Yang J, Roe SM, Cliff MJ, Williams MA, Ladbury JE, Cohen PT, Barford D, EMBO J. 2005 Jan 12;24(1):1-10. Epub 2004 Dec 2. PMID:15577939

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