1i9z

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Template:STRUCTURE 1i9z

CRYSTAL STRUCTURE OF INOSITOL POLYPHOSPHATE 5-PHOSPHATASE DOMAIN (IPP5C) OF SPSYNAPTOJANIN IN COMPLEX WITH INOSITOL (1,4)-BISPHOSPHATE AND CALCIUM ION

Overview

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.

About this Structure

1I9Z is a Single protein structure of sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA.

Reference

Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase., Tsujishita Y, Guo S, Stolz LE, York JD, Hurley JH, Cell. 2001 May 4;105(3):379-89. PMID:11348594 Page seeded by OCA on Fri May 2 19:45:24 2008