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dc.contributor.advisorSarah E. O'Connor.en_US
dc.contributor.authorHillmann, William C. (William Carmen)en_US
dc.contributor.otherMassachusetts Institute of Technology. Dept. of Chemistry.en_US
dc.date.accessioned2008-12-11T18:31:51Z
dc.date.available2008-12-11T18:31:51Z
dc.date.copyright2008en_US
dc.date.issued2008en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/43812
dc.descriptionThesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008.en_US
dc.descriptionVita.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractNatural products are a rich source of medicinally important molecules. Monoterpene indole alkaloids from plants are an especially important source of therapeutic molecules. Due to the complexity of these molecules, biosynthesis of derivatives is an attractive way of obtaining molecules with potentially new or improved functionality. The rational design of mutants with altered/expanded substrate scope is an important step in engineering organisms to produce such compounds. In monoterpene indole alkaloid biosynthesis, the enzyme strictosidine synthase catalyzes the first committed reaction. This reaction is a Pictet-Spengler coupling between tryptamine and secologanin and produces the biosynthetic intermediate strictosidine, common to all monoterpene indole alkaloids. To better understand the structural features that impart binding selectivity, crystallization studies of this enzyme were performed. The native enzyme and several interesting mutants were studied; co-crystallization experiments with inhibitors and substrates were also performed. Diffraction quality crystals of the native enzyme were obtained following optimization by grid screening, additive screens, and macroseeding. Data on the optimized crystals was collected at the Argonne National Labs synchrotron radiation source. In addition to monoterpene indole alkaloids, the benzylisoquinoline alkaloids are another class of medicinally important plant derived natural products. In a reaction analogous to that catalyzed by strictosidine synthase, the first committed step of benzylisoquinoline biosynthesis is a Pictet-Spengler reaction between 4-hydroxyphenylactetaldehyde and dopamine, catalyzed by the enzyme norcoclaurine synthase. Two different forms of this enzyme have been identified, neither of which shows any homology to strictosidine synthase.en_US
dc.description.abstract(cont.) Structural information for these enzymes could provide general structural features required for enzymatic Pictet-Spengler reactions. Before crystallization, the enzymes were expressed and tested for activity. Once active preparations of protein were available, crystallization studies were performed and crystals were obtained.en_US
dc.description.statementofresponsibilityby William C. Hillmann.en_US
dc.format.extent109 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.titleCrystallization studies of Pictet-Spenglerasesen_US
dc.typeThesisen_US
dc.description.degreeS.M.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistry
dc.identifier.oclc262478252en_US


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