3NR8

Crystal structure of human SHIP2

Summary for 3NR8

• Entry DOI: 10.2210/pdb3nr8/pdb
• Related: 3MTC 3N9V
• Descriptor: Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2, CHLORIDE ION (3 entities in total)
• Functional Keywords: structural genomics consortium, sgc, phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 2, ship2, inppl1, ship-2, phosphatidylinositol, phosphatase, signalling, magnesium, structural genomics consortium stockholm, magnesium binding, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol: O15357
• Total number of polymer chains: 2
• Total formula weight: 72523.16

Authors

Tresaugues, L.,Welin, M.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Collins, R.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, I.,Karlberg, T.,Kol, S.,Kotenyova, T.,Kouznetsova, E.,Moche, M.,Nyman, T.,Persson, C.,Schuler, H.,Schutz, P.,Siponen, M.I.,Thorsell, A.G.,van der Berg, S.,Wahlberg, E.,Weigelt, J.,Nordlund, P.,Structural Genomics Consortium (SGC) (deposition date: 2010-06-30, release date: 2010-08-25, Last modification date: 2023-09-06)

Primary citation

Tresaugues, L.,Silvander, C.,Flodin, S.,Welin, M.,Nyman, T.,Graslund, S.,Hammarstrom, M.,Berglund, H.,Nordlund, P.
Structural basis for phosphoinositide substrate recognition, catalysis, and membrane interactions in human inositol polyphosphate 5-phosphatases
Structure, 22:744-755, 2014

PubMed Abstract: SHIP2, 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.

PubMed: 24704254
DOI: 10.1016/j.str.2014.01.013

Experimental method

X-RAY DIFFRACTION (2.8 Å)