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.
Keywords:
Lowe syndrome; Myotubularin; OCRL; PTEN; Sac1.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Bacteria / chemistry
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Bacteria / enzymology
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Bacterial Proteins / chemistry*
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Bacterial Proteins / metabolism
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Biocatalysis
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Cell Membrane / chemistry
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Cell Membrane / metabolism
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Crystallography, X-Ray
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Genetic Diseases, X-Linked / enzymology
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Genetic Diseases, X-Linked / genetics
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Genetic Diseases, X-Linked / pathology
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Humans
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Inositol Polyphosphate 5-Phosphatases
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Isoenzymes / chemistry
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Isoenzymes / metabolism
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism
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Models, Molecular
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Nephrolithiasis / enzymology
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Nephrolithiasis / genetics
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Nephrolithiasis / pathology
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Oculocerebrorenal Syndrome / enzymology
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Oculocerebrorenal Syndrome / genetics
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Oculocerebrorenal Syndrome / pathology
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PTEN Phosphohydrolase / chemistry*
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PTEN Phosphohydrolase / metabolism
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Phosphatidylinositols / chemistry
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Phosphatidylinositols / metabolism
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Phosphoric Monoester Hydrolases / chemistry*
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Phosphoric Monoester Hydrolases / metabolism
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Protein Tyrosine Phosphatases, Non-Receptor / chemistry*
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Protein Tyrosine Phosphatases, Non-Receptor / metabolism
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Substrate Specificity
Substances
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Bacterial Proteins
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Isoenzymes
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Membrane Proteins
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Phosphatidylinositols
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Sac1 protein, mammalian
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Phosphoric Monoester Hydrolases
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Protein Tyrosine Phosphatases, Non-Receptor
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myotubularin
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Inositol Polyphosphate 5-Phosphatases
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PTEN Phosphohydrolase