Using macromolecular neutron crystallography to study hydrogen atoms in the catalytic mechanism of the FADH cofactor in cholesterol oxidase

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dc.contributor.authorGolden, Een_AU
dc.contributor.authorYu, LJen_AU
dc.contributor.authorMeilleur, Fen_AU
dc.contributor.authorBlakeley, MPen_AU
dc.contributor.authorDuff, APen_AU
dc.contributor.authorKarton, Aen_AU
dc.contributor.authorVrielink, Aen_AU
dc.date.accessioned2021-08-17T02:58:04Zen_AU
dc.date.available2021-08-17T02:58:04Zen_AU
dc.date.issued2017-07-12en_AU
dc.date.statistics2021-08-10en_AU
dc.description.abstractThe protein microenvironment surrounding the flavin cofactor in flavoenzymes is key to the efficiency and diversity of reactions catalysed by this class of enzymes. X-ray diffraction structures of oxidoreductase flavoenzymes have revealed recurrent features which facilitate catalysis, such as a hydrogen bond between a main chain nitrogen atom and the flavin redox center (N5). A neutron diffraction study of cholesterol oxidase has revealed an unusual elongated main chain nitrogen to hydrogen bond distance positioning the hydrogen atom towards the flavin N5 reactive center. Investigation of the structural features which could cause such an unusual occurrence revealed a positively charged lysine side chain, conserved in other flavin mediated oxidoreductases, in a second shell away from the FAD cofactor acting to polarize the peptide bond through interaction with the carbonyl oxygen atom. Double-hybrid density functional theory calculations confirm that this electrostatic arrangement affects the N-H bond length in the region of the flavin reactive center. We propose a novel second-order partial-charge interaction network which enables the correct orientation of the hydride receiving orbital of N5. The implications of these observations for flavin mediated redox chemistry are discussed.en_AU
dc.identifier.citationGolden, E., Yu, L.-J., Meilleur, F., Blakeley, M., Duff, A., Karton, A., & Vrielink, A. (2017). Using macromolecular neutron crystallography to study hydrogen atoms in the catalytic mechanism of the FADH cofactor in cholesterol oxidase. Paper presented at ICNS 2017 (International Conference on Neutron Scattering), Daejeon, South Korea, 9 to 13 July 2017. Retrieved from: http://www.icns2017.org/program.phpen_AU
dc.identifier.conferenceenddate13 July 2017en_AU
dc.identifier.conferencenameICNS 2017 (International Conference on Neutron Scattering)en_AU
dc.identifier.conferenceplaceDaejeon, South Koreaen_AU
dc.identifier.conferencestartdate9 July 2017en_AU
dc.identifier.urihttp://www.icns2017.org/program.phpen_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/11377en_AU
dc.language.isoenen_AU
dc.publisherInternational Conference on Neutron Scatteringen_AU
dc.subjectProteinsen_AU
dc.subjectIsoalloxazinesen_AU
dc.subjectEnzymesen_AU
dc.subjectX-ray diffractionen_AU
dc.subjectOxidoreductasesen_AU
dc.subjectNeutron diffractionen_AU
dc.subjectCholesterolen_AU
dc.titleUsing macromolecular neutron crystallography to study hydrogen atoms in the catalytic mechanism of the FADH cofactor in cholesterol oxidaseen_AU
dc.typeConference Abstracten_AU
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