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dc.creatorHoward, Alicia L.
dc.date.available2012-06-01T15:24:39Z
dc.date.issued2011-08
dc.identifier.urihttp://hdl.handle.net/2346/ETD-TTU-2011-08-1841
dc.description.abstractThe role of the sterol C3-hydroxyl group of lanosterol in the reaction catalyzed by Paracoccidioides brasiliensis sterol C24-methyltransferase (PbSMT) was studied kinetically and for product differences against a panel of modified lanosterol C3-derivatives in which the natural C3β-OH was chemically replaced with α-OH, OMe, OAc, keto, NH₂, F, H and NH₃⁺. PbSMT catalyzed variably 7 test substrates that retained nucleophilic character whereas neither the 3-desoxy nor the salt analogs were productively bound. GC-MS analysis of the biomethyl products catalyzed by PbSMT showed similar recognition of the sterol side chain; each of them contained the same Δ²⁴⁽²⁸⁾- construction. Alternatively, significant differences in the catalytic competence (Vmax/ Km) of the analogs tested revealed sterol-specific Michaelis complexes resulting from the differences associated with the size, electronics and configuration of the substrate C3-group. These results revealed that polarity and stereochemistry of the C3-group is essential in the enzyme-substrate interactions of PbSMT and that the 3β-OH group is the best structural feature tested for optimal activity.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.subjectC24 sterol methyltransferase
dc.subjectParacoccidioides brasiliensis
dc.subjectC3-OH, Hydrogen bonding
dc.titleProbing the role of the 3-hydroxy group of lanosterol in substrate-enzyme interactions of the Paracoccidioides brasiliensis sterol C24-methyltransferase
dc.typeThesis
thesis.degree.nameMaster of Science
thesis.degree.levelMasters
thesis.degree.disciplineBiochemistry
thesis.degree.grantorTexas Tech University
thesis.degree.departmentChemistry
thesis.degree.departmentChemistry and Biochemistry
dc.contributor.committeeMemberWeber, Joachim
dc.contributor.committeeChairNes, William David
dc.degree.departmentChemistry
dc.rights.availabilityUnrestricted.


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