Structural Basis for Phosphoinositide Substrate Recognition, Catalysis, and Membrane Interactions in Human Inositol Polyphosphate 5-Phosphatases
| Autor: | Martin Welin, Susanne Gräslund, Helena Berglund, Martin Hammarström, Camilla Silvander, Tomas Nyman, Susanne Flodin, Pär Nordlund, Lionel Trésaugues |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Polyphosphate Inositol Phosphates Cell Membrane Substrate (chemistry) Biology Crystallography X-Ray Phosphatidylinositols Phosphoric Monoester Hydrolases Catalysis Substrate Specificity chemistry.chemical_compound Membrane Biochemistry chemistry Structural Biology Catalytic Domain Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Hydrolase Humans OCRL Inositol Lipid bilayer Molecular Biology |
| Zdroj: | Structure. 22(5):744-755 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2014.01.013 |
| Popis: | SummarySHIP2, OCRL, and INPP5B belong to inositol polyphosphate 5-phophatase subfamilies involved in insulin regulation and Lowes syndrome. The structural basis for membrane recognition, substrate specificity, and regulation of inositol polyphosphate 5-phophatases is still poorly understood. We determined the crystal structures of human SHIP2, OCRL, and INPP5B, the latter in complex with phosphoinositide substrate analogs, which revealed a membrane interaction patch likely to assist in sequestering substrates from the lipid bilayer. Residues recognizing the 1-phosphate of the substrates are highly conserved among human family members, suggesting similar substrate binding modes. However, 3- and 4-phosphate recognition varies and determines individual substrate specificity profiles. The high conservation of the environment of the scissile 5-phosphate suggests a common reaction geometry for all members of the human 5-phosphatase family. |
| Databáze: | OpenAIRE |
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