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dc.contributor.advisor York, John D. en_US
dc.contributor.author Endo-Streeter, Stuart Tamotsu en_US
dc.date.accessioned 2009-12-18T16:25:20Z
dc.date.available 2009-12-18T16:25:20Z
dc.date.issued 2009 en_US
dc.identifier.uri http://hdl.handle.net/10161/1608
dc.description Dissertation en_US
dc.description.abstract <p>Inositol Polyphosphate Multi-Kinase (IPMK, also known as ArgRIII, Arg82, and IPK2) is a central component of the inositol signaling system, catalyzing the phosphorylation of at least four different inositol polyphosphate species in vivo with in vitro activity observed for three more. Each of these IP species is sterically unique and the phosphorylation target varies between the 6'-, 3'-, or 5'-hydroxyls, classifying IPMK as a 6/3/5-kinase. The products of IPMK have been linked to multiple processes including cell cycle regulation, transcriptional control, telomere length regulation, mRNA export and various phenotypes including mouse embryonic and fly larvae development, and stress responses in plants and yeast. Linking specific IP species and cellular processes has been complicated by the inability to distinguish between the different effects of the various IP species generated by IPMK. Deletion of IPMK affects the IP populations of all its various substrates and products and therefore the role of a single IP species cannot be tracked. The goals of this work were to address the question of substrate selectivity and develop new tools to probe inositol signaling in vivo through a combination of structural, enzymatic, and genomic techniques.</p><p>The structure of Arabidopsis thaliana IPMK is reported at 2.9Å resolution and in conjunction with a new model of inositol selectivity has been used to design constructs with altered substrate profiles. In vitro and in vivo experiments have confirmed that IPMK identifies substrate inositol polyphosphate species through a recognition surface that requires phosphate groups occupy specific pockets and rejects those with axial phosphate groups in specific regions. In vivo experiments have linked specific inositol polyphosphate species to nitrogen metabolism and temperature sensitivity in yeast and established the potential for these constructs to be used to probe signaling in other organisms.</p> en_US
dc.format.extent 5807094 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Chemistry, Biochemistry en_US
dc.subject Biophysics, General en_US
dc.subject Biology, Molecular en_US
dc.subject Design en_US
dc.subject Inositol en_US
dc.subject Kinase en_US
dc.subject Signaling en_US
dc.subject Structure en_US
dc.title Structural Studies of Arabidopsis Thaliana Inositol Polyphosphate Multi-Kinase en_US
dc.type Dissertation en_US
dc.department Biochemistry en_US
duke.embargo.months 12 en_US
dc.date.accessible 2010-05-18T05:00:26Z

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