Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase.
Journal Article (Journal Article)
Inositol polyphosphate 5-phosphatases are central to intracellular processes ranging from membrane trafficking to Ca(2+) signaling, and defects in this activity result in the human disease Lowe syndrome. The 1.8 resolution structure of the inositol polyphosphate 5-phosphatase domain of SPsynaptojanin bound to Ca(2+) and inositol (1,4)-bisphosphate reveals a fold and an active site His and Asp pair resembling those of several Mg(2+)-dependent nucleases. Additional loops mediate specific inositol polyphosphate contacts. The 4-phosphate of inositol (1,4)-bisphosphate is misoriented by 4.6 compared to the reactive geometry observed in the apurinic/apyrimidinic endonuclease 1, explaining the dephosphorylation site selectivity of the 5-phosphatases. Based on the structure, a series of mutants are described that exhibit altered substrate specificity providing general determinants for substrate recognition.
Full Text
Duke Authors
Cited Authors
- Tsujishita, Y; Guo, S; Stolz, LE; York, JD; Hurley, JH
Published Date
- May 4, 2001
Published In
Volume / Issue
- 105 / 3
Start / End Page
- 379 - 389
PubMed ID
- 11348594
International Standard Serial Number (ISSN)
- 0092-8674
Digital Object Identifier (DOI)
- 10.1016/s0092-8674(01)00326-9
Language
- eng
Conference Location
- United States