The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function

Franco-Echevarría, Elsa, Sanz-Apricio, Julia, Brearley, Charles A., González-Rubio, Juana M and González, Beatriz (2017) The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function. The Journal of Biological Chemistry, 292 (25). pp. 10534-10548. ISSN 0021-9258

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    Abstract

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinases (IP5 2-Ks) comprise a family of enzymes in charge of synthesizing inositol hexakisphosphate (IP6) in eukaryotic cells. This protein and its product IP6 present many roles in cells, participating in mRNA export, embryonic development, and apoptosis. We reported previously that the full-length IP5 2-K from Arabidopsis thaliana (At) is a zinc metallo-enzyme including two separated lobes (the N and C lobes). We have also shown conformational changes in IP5 2-K and have identified the residues involved in substrate recognition and catalysis. However, the specific features of mammalian IP5 2-Ks remain unknown. To this end, we report here the first structure for a murine IP5 2-K in complex with ATP/IP5 or IP6. Our structural findings indicated that the general folding in N and C lobes is conserved with AtIP5 2-K. A helical scaffold in the C lobe constitutes the inositol phosphate (IP)-binding site, which, along with the participation of the N lobe, endows high specificity to this protein. However, we also noted large structural differences between the orthologous from these two eukaryotic kingdoms. These differences include a novel zinc-binding site and regions unique to the mammalian IP5 2-K, as an unexpected basic patch on the protein surface. In conclusion, our findings have uncovered distinct features of a mammalian IP5 2-K and set the stage for investigations into protein-protein or protein-RNA interactions important for IP5 2-K function and activity.

    Item Type: Article
    Uncontrolled Keywords: crystal structure,enzyme mutation,inositol phosphate,structure-function,zinc ip5 2-kinase,inositol hexakisphosphate
    Faculty \ School: Faculty of Science > School of Biological Sciences
    University of East Anglia > Faculty of Science > Research Groups > Plant Sciences
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    Depositing User: Pure Connector
    Date Deposited: 03 May 2017 06:10
    Last Modified: 25 Jul 2018 13:34
    URI: https://ueaeprints.uea.ac.uk/id/eprint/63350
    DOI: 10.1074/jbc.M117.780395

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