NASA Logo

NTRS

NTRS - NASA Technical Reports Server

Back to Results
Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.
Document ID
20040085935
Acquisition Source
Marshall Space Flight Center
Document Type
Preprint (Draft being sent to journal)
Authors
Swingle, Mark R.
(University of South Alabama Mobile, AL, United States)
Ciszak, Ewa M.
(NASA Marshall Space Flight Center Huntsville, AL, United States)
Honkanen, Richard E.
(University of South Alabama Mobile, AL, United States)
Date Acquired
August 21, 2013
Publication Date
January 1, 2004
Subject Category
Life Sciences (General)
Meeting Information
Meeting: Federation of American Societies for Experimental Biology
Location: Snowman Village, CO
Country: United States
Start Date: July 17, 2004
End Date: July 22, 2004
Sponsors: Federation of American Societies for Experimental Biology
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.

Available Downloads

There are no available downloads for this record.
No Preview Available