title: Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5.
abstract: Serine/threonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell growth and cellular responses to stress. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A. 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 Asp271-M1:M2-W1-His427-His304-Asp274 catalytic motif (where M1 and M2 are metals and W1 is a water molecule). The structure of PP5c provides a 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama 36688, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Swingle
authors.forename: Richard E
authors.initials: RE
authors.lastname: Honkanen
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Ciszak
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D017124:Conserved Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D015870:Gene Expression; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D009687:Nuclear Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5