title: The structure of phosphoinositide phosphatases: Insights into substrate specificity and catalysis.
abstract: Phosphoinositides (PIs) are a group of key signaling and structural lipid molecules involved in a myriad of cellular processes. PI phosphatases, together with PI kinases, are responsible for the conversion of PIs between distinctive phosphorylation states. PI phosphatases are a large collection of enzymes that are evolved from at least two disparate ancestors. One group is distantly related to endonucleases, which apply divalent metal ions for phosphoryl transfer. The other group is related to protein tyrosine phosphatases, which contain a highly conserved active site motif Cys-X5-Arg (CX5R). In this review, we focus on structural insights to illustrate current understandings of the molecular mechanisms of each PI phosphatase family, with emphasis on their structural basis for substrate specificity determinants and catalytic mechanisms. This article is part of a Special Issue entitled Phosphoinositides.
authors.affiliation: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: FoSheng
authors.initials: F
authors.lastname: Hsu
authors.affiliation: Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: ym253@cornell.edu.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D001419:Bacteria / Q000737:chemistry / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D040181:Genetic Diseases, X-Linked / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D053040:Nephrolithiasis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009800:Oculocerebrorenal Syndrome / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000737:chemistry* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D010716:Phosphatidylinositols; C416669:Sac1 protein, mammalian; D010744:Phosphoric Monoester Hydrolases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin; D000072181:Inositol Polyphosphate 5-Phosphatases; D051059:PTEN Phosphohydrolase
keywords: Lowe syndrome; Myotubularin; OCRL; PTEN; Sac1