Expression, Purification and Analysis of Recombinant 3Beta Hydroxy-Sterol Dehydrogenase (NSDHL): A Potential Farnesol Dehydrogenase

Faculty Mentor Information

Ken Cornell Ph.D

Presentation Date

7-2017

Abstract

Mutations in the NSDHL gene, which encodes the cholesterol biosynthetic enzyme 3beta hydroxyl-sterol dehydrogenase, are responsible for rare X-linked congenital disorders like CHILD syndrome. The membrane bound enzyme potentially performs a previously unidentified farnesol dehydrogenase activity to catalyze the transformation of the isoprenyl alcohol farnesol to the isoprenyl aldehyde farnesal. To test this hypothesis, we have expressed and purified recombinant full length, truncated, and mutated forms of the enzyme. The enzymes will be analyzed for activity using spectrofluorimetric assays to assess substrate specificity and catalytic rates. Our results may illuminate novel roles for farnesol in the pathology of rare X-linked disorders like CHILD syndrome and may be valuable in the development of novel treatments for this disease.

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Expression, Purification and Analysis of Recombinant 3Beta Hydroxy-Sterol Dehydrogenase (NSDHL): A Potential Farnesol Dehydrogenase

Mutations in the NSDHL gene, which encodes the cholesterol biosynthetic enzyme 3beta hydroxyl-sterol dehydrogenase, are responsible for rare X-linked congenital disorders like CHILD syndrome. The membrane bound enzyme potentially performs a previously unidentified farnesol dehydrogenase activity to catalyze the transformation of the isoprenyl alcohol farnesol to the isoprenyl aldehyde farnesal. To test this hypothesis, we have expressed and purified recombinant full length, truncated, and mutated forms of the enzyme. The enzymes will be analyzed for activity using spectrofluorimetric assays to assess substrate specificity and catalytic rates. Our results may illuminate novel roles for farnesol in the pathology of rare X-linked disorders like CHILD syndrome and may be valuable in the development of novel treatments for this disease.