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dc.contributor.advisorCatherine L. Drennan.en_US
dc.contributor.authorJonnalagadda, Rohan.en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Biology.en_US
dc.date.accessioned2020-09-03T17:48:22Z
dc.date.available2020-09-03T17:48:22Z
dc.date.copyright2020en_US
dc.date.issued2020en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/127130
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, May, 2020en_US
dc.descriptionCataloged from the official PDF of thesis. Vita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractBiological systems use iron as a key cofactor to catalyze a variety of difficult chemical transformations, particularly as reservoirs from which to initiate enzymatic radical chemistry. Here, I discuss efforts to study the allosteric mechanisms of an essential human iron and free radical utilizing enzyme: ribonucleotide reductase (RNR), and efforts to elucidate the radical based mechanism of isonitrile formation by an mononuclear nonheme iron(II) α-ketoglutarate dependent dioxygenase, ScoE. The first part of this thesis focuses on mononuclear nonheme iron(II) α-ketoglutarate dependent dioxygenases: enzymes which use molecular oxygen, α-ketoglutarate and a mononuclear Fe(II) cofactor to initiate substrate radical chemistry and catalyze diverse chemistries such as hydroxylations, halogenations and desaturations. Chapter 1 of this thesis describes current understanding of the mechanisms of these enzymes. Chapter 2 describes biochemical and structural efforts to determine the catalytic mechanism of one member of these enzymes: the isonitrile formation enzyme ScoE. In the chapter 3 of this thesis, I discuss the structure, function and allosteric regulation of RNR, the sole known enzyme capable of catalyzing the de novo biosynthesis of deoxyribonucleotides in all organisms for use in DNA replication and repair. Chapter 4 concerns efforts to develop a procedure for the improved recombinant protein yield of human RNR, and chapter 5 describes the development of a new liquid chromatography-tandem mass spectrometry based assay for RNR activity that we propose holds promise for simultaneous detection of RNR activity on multiple substrates.en_US
dc.description.statementofresponsibilityby Rohan Jonnalagadda.en_US
dc.format.extent162 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectBiology.en_US
dc.titleStructural and functional investigations of mechanisms of iron-utilizing enzymesen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.identifier.oclc1191837325en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Biologyen_US
dspace.imported2020-09-03T17:48:22Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentBioen_US


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