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dc.contributor.advisorCatherine L. Drennan.en_US
dc.contributor.authorBerkovitch, Frederick, 1978-en_US
dc.contributor.otherMassachusetts Institute of Technology. Dept. of Chemistry.en_US
dc.date.accessioned2005-09-27T17:50:11Z
dc.date.available2005-09-27T17:50:11Z
dc.date.copyright2004en_US
dc.date.issued2004en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/28698
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.en_US
dc.descriptionVita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstract(cont.) in the same pathway. To further probe the relationship of the adenosylmethionine and adenosylcobalamin-dependent radical enzymes, the crystal structure of lysine 5,6-aminomutase was determined to 2.8 [angstroms] resolution. Like biotin synthase, the structure of lysine-5,6-aminomutase adheres to the general theme of barrels or barrel-like structures for enzymes that utilize 5'-deoxyadenosyl radicals in catalysis. Additionally, the structure of lysine-5,6-aminomutase implicates pyridoxal phosphate in a novel role, acting as a lock to prevent the formation of aberrant radicals in the absence of substrate.en_US
dc.description.abstract"AdoMet radical" enzymes utilize a 4Fe-4S cluster and S-adenosylmethionine, in conjunction with a reducing system, to catalyze reactions that proceed through organic radical intermediates. Genomics studies suggest that at least 600 such enzymes exist across the archaea, bacteria, and eukaryotes, though few have been purified and characterized. AdoMet radical enzymes participate in several biomedically important processes, such as DNA biosynthesis and repair, cofactor biosynthesis, and bacterial pathogenesis. To gain insight into this enzyme family, the crystal structure biotin synthase from Escherichia coli, in complex with its substrate dethiobiotin, was determined to 3.4 [angstrom] resolution. Biotin synthase catalyzes a remarkable reaction, the insertion of sulfur into dethiobiotin to form biotin (vitamin B₈). The structure of biotin synthase indicates that adenosylmethionine is coordinated to a unique Fe of the 4Fe-4S cluster, in agreement with spectroscopic investigations from other laboratories. Additionally, the structure reveals that the active site, located in the core of an (α/β)₈ barrel, contains a unique 2Fe-2S cluster, in addition to the 4Fe-4S cluster, adenosylmethionine, and dethiobiotin. Multiple lines of evidence suggest that in the AdoMet radical enzymes, adenosylmethionine is a source of 5'-deoxyadenosyl radical, an intermediate that is historically associated with the adenosylcobalamin-dependent radical enzymes. Interestingly, some of the adenosylcobalamin radical enzymes catalyze reactions that are very similar to those of AdoMet radical enzymes. One such example is adenosylcobalamin-dependent lysine 5,6-aminomutase, which is analogous to lysine 2,3-aminomutase, an AdoMet radical enzyme that is founden_US
dc.description.statementofresponsibilityby Frederick Berkovitch.en_US
dc.format.extent175 leavesen_US
dc.format.extent8815145 bytes
dc.format.extent8837452 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.language.isoen_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/1721.1/7582
dc.subjectChemistry.en_US
dc.titleSnapshots of radical enzyme catalysis : the crystal structures of biotin synthase and lysine 5,6-aminomutaseen_US
dc.title.alternativeCrystal structures of biotin synthase and lysine 5,6-aminomutaseen_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Dept. of Chemistry.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.identifier.oclc59133070en_US


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