Determination of the Binding Mode of Hydroxycitrate, and Investigation of the Binding Site of 14-3-3 Protein on Human ATP Citrate Lyase

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atmire.migration.oldid5210
dc.contributor.advisorFraser, Marie
dc.contributor.authorHu, Jinhong
dc.contributor.committeememberMoorhead, Greg
dc.contributor.committeememberZaremberg, Vanina
dc.date.accessioned2017-01-06T18:44:29Z
dc.date.available2017-01-06T18:44:29Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractATP citrate lyase (ACLY) catalyzes the reaction: citrate + CoA + ATP → acetyl-CoA + oxaloacetate +ADP + Pi (Srere & Lipmann, 1953). Because acetyl-CoA is the precursor of de novo lipogenesis, human ACLY (hACLY) is linked to multiple diseases (Groot et al., 2003; Bauer et al., 2005). The goal of this study is to understand the catalytic and regulatory mechanism of hACLY. Crystals of a rationally designed form of the amino terminus of hACLY showed electron density of the catalytic loop for the first time. The binding modes of the inhibitors, 4R- and 4S-hydroxycitrate, were seen, and it was concluded that either the hydroxycitryl-CoA cannot be formed or cannot be cleaved. Binding assays were done to determine whether 14-3-3 protein binds directly to phosphorylated serine-455 of hACLY. The results suggest that 14-3-3 protein binds to hACLY, but not specific ally to phosphorylated Ser-455.en_US
dc.identifier.citationHu, J. (2017). Determination of the Binding Mode of Hydroxycitrate, and Investigation of the Binding Site of 14-3-3 Protein on Human ATP Citrate Lyase (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25607en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/25607
dc.identifier.urihttp://hdl.handle.net/11023/3549
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology
dc.titleDetermination of the Binding Mode of Hydroxycitrate, and Investigation of the Binding Site of 14-3-3 Protein on Human ATP Citrate Lyase
dc.typemaster thesis
thesis.degree.disciplineBiological Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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