Probing the role of the 3-hydroxy group of lanosterol in substrate-enzyme interactions of the Paracoccidioides brasiliensis sterol C24-methyltransferase

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Title: Probing the role of the 3-hydroxy group of lanosterol in substrate-enzyme interactions of the Paracoccidioides brasiliensis sterol C24-methyltransferase
Author: Howard, Alicia L.
Abstract: The 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 .
URI: http : / /hdl .handle .net /2346 /ETD -TTU -2011 -08 -1841
Date: 2011-08

Citation

Probing the role of the 3-hydroxy group of lanosterol in substrate-enzyme interactions of the Paracoccidioides brasiliensis sterol C24-methyltransferase. Master's thesis, Texas Tech University. Available electronically from http : / /hdl .handle .net /2346 /ETD -TTU -2011 -08 -1841 .

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