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dc.contributor.advisorCatherine L. Drennan.en_US
dc.contributor.authorWong, Cintyuen_US
dc.contributor.otherMassachusetts Institute of Technology. Dept. of Chemistry.en_US
dc.date.accessioned2009-11-06T16:29:27Z
dc.date.available2009-11-06T16:29:27Z
dc.date.copyright2009en_US
dc.date.issued2009en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/49749
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009.en_US
dc.descriptionVita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractCofactors assist enzymes with a variety of complex chemistries. Two versatile cofactors, flavin adenine dinucleotide (FAD) and non-heme iron, together with molecular oxygen as an oxidizing agent, perform a wide array of reactions. Hydroxylation in DNA repair is one example. AidB is an adaptive response protein that is up-regulated in the presence of alkylating agents. AidB contains FAD; however, the precise role of the FAD has been determined. AlkB, another adaptive response protein that is up-regulated in the presence of alkylating agents, is a member of the alpha-ketoglutarate (aKG) non-heme iron-dependent superfamily. It uses the cofactor non-heme iron, and the co-substrates molecular oxygen a: G, to remove alkylated adducts on DNA bases via hydroxylation. Two well characterized 1 homologues of AlkB, hABH2 and hABH3, also belong to the XKG/Fe(II)-dependent superfamily, but their substrate preference differ from that of AlkB. Furthermore, FAD and non-heme iron, again with molecular oxygen as an oxidizing agent, can perform halogenation chemistry. Flavin-dependent halogenasess perform halogenation reactions on aromatic substrates, while non-heme iron-dependent halogenases perform halogenations reactions on unactivated aliphatic substrates. I is a flavin-dependent halogenase that catalyzes the chlorination of free tryptophan to form 7-chlorotryptophan in the biosynthesis of rebeccamycin. CytC3 is an cxKG and non-heme iron-dependent halogenase that catalyzes the chlorination of L-2-aminobutyric acid bound to thiolation domain in the biosynthesis of yy-dichloroaminobutyrate.en_US
dc.description.abstract(cont.) Here, we obtained the crystal structures of flavoproten I and non-heme iron-dependent halogenase CytC3. The structural and biochemical v n AidB provides new insights into various possible functions of this still poorly understood protein. The crystal structure of CytC3 suggests two important criteria for creating an enzyme--bound Fe-Cl catalyst. Additionally, we established a new purification scheme for AlkB ts human homologues, which has yielded protein for biochemical studies aimed at ex i ; substrate specificity. Finally, we have also obtained a new crystal form for E. coli AlkB.en_US
dc.description.statementofresponsibilityby Cintyu Wong.en_US
dc.format.extent211 p.en_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemistry.en_US
dc.titleTwo versatile cofactors, flavin adenine dinucleotide and non-heme iron, involved in DNA repair and natural product halogenationen_US
dc.title.alternative2 versatile cofactors, flavin adenine dinucleotide and non-heme iron, involved in DNA repair and natural product halogenationen_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.identifier.oclc456555677en_US


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