title: Interactor-guided dephosphorylation by protein phosphatase-1.
abstract: Protein phosphatase-1 (PP1) is an essential enzyme for every eukaryotic cell and catalyzes more than half of all protein dephosphorylations at serine and threonine residues. The free catalytic subunit of PP1 shows little substrate selectivity but is tightly regulated in vivo by a large variety of structurally unrelated PP1-interacting proteins (PIPs). PIPs form highly specific dimeric or trimeric PP1 holoenzymes by acting as substrates, inhibitors, and/or substrate-specifiers. The surface of PP1 contains many binding sites for short PP1-docking motifs that are combined by PIPs to create a PP1-binding code that is universal, specific, degenerate, nonexclusive, and dynamic. These properties of the PP1-binding code can be used for the rational design of small molecules that disrupt subsets of PP1 holoenzymes and have a therapeutic potential.
authors.affiliation: Laboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Shannah
authors.initials: S
authors.lastname: Boens
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Szekér
authors.forename: Aleyde
authors.initials: A
authors.lastname: Van Eynde
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D020035:Holoenzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D020035:Holoenzymes; D054645:Protein Phosphatase 1