کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2029731 | 1070960 | 2014 | 12 صفحه PDF | دانلود رایگان |
• Structures of INPP5B/phosphoinositide complexes reveal substrate determinants
• Confirmation of the shared catalytic mechanism with AP endonucleases
• Determination of the membrane interacting regions
• Major differences with the previous model based upon SPsynaptojanin
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.
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Journal: - Volume 22, Issue 5, 6 May 2014, Pages 744–755