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dc.contributor.advisorCatherine L. Drennan.en_US
dc.contributor.authorKang, Gyunghoon.en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemistry.en_US
dc.date.accessioned2020-01-23T16:57:03Z
dc.date.available2020-01-23T16:57:03Z
dc.date.copyright2019en_US
dc.date.issued2019en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/123568
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019en_US
dc.descriptionCataloged from PDF version of thesis. Vita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractRibonucleotide reductase (RNR) catalyzes the reduction of nucleotides to their 2'-deoxynucleotide counterparts. The class la RNR from Escherichia coli is composed of two homodimeric subunits [alpha]2 and [beta]2 that form an [alpha]2[beta]2 complex to perform nucleotide reduction. Chemistry is initiated by a thiyl-radical (C439·) in the active site of [beta]2 that is reversibly generated by a diferric-tyrosyl radical cofactor (Y122·) in [beta]2 by a series of proton-coupled electron transfer steps: Y122[beta] <-> [W48[beta]] <-> Y356[beta] <-> Y731[alpha] - Y730[alpha] - C439[alpha]. A high-resolution structure of the active [alpha]2[beta]2 complex has long eluded the field due to the weak and transient nature of the a2-P2 interaction. Previous studies revealed that perturbing radical transfer by incorporating unnatural amino acids along the transfer pathway, or by using mechanistic inhibitors that trap the radical in the active site, can extend the lifetime of the [alpha]2[beta]2 complex, allowing for structural studies. Here, we present our efforts to study the E. coli class la RNR [alpha]2[beta]2 complex, trapped using these different perturbation methods, using cryo-electron microscopy. The two [alpha]2[beta]2 structures presented here provide deeper insight into the structural dynamics of nucleotide reduction. We end with a brief discussion of class la RNR from T4 bacteriophage, which despite sharing high sequence identity to its host E. coli class la RNR, employs a very different mode of oligomeric regulation.en_US
dc.description.statementofresponsibilityby Gyunghoon Kang.en_US
dc.format.extent178 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemistry.en_US
dc.titleStructural investigations of class la ribonucleotide reductases by electron microscopyen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.identifier.oclc1135348734en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Chemistryen_US
dspace.imported2020-01-23T16:57:02Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentChemen_US


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