Scientists at Case Western University, under the support in part by the Public Health Service Grant, was able to map the allosteric site in Cholesterol Hydroxylase CYP46A1 for efavirenz, a drug used to treat HIV infections, that stimulates enzyme activity.
Scientists at Case Western University, under the support in part by the Public Health Service Grant, was able to map the allosteric site in Cholesterol Hydroxylase CYP46A1 for efavirenz, a drug used to treat HIV infections, that stimulates enzyme activity.
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What they Found
CYP46A1 is an enzyme responsible for 80 percent of the cholesterol breakdown in the human brain. Efavirenz attaches to this enzyme and speeds up its activity. A cutting-edge atom substitution technology called hydrogen-deuterium exchange (HDX) allowed them to see this. It is now the key evidence in the Irina Pikuleva's team's proposal to launch clinical trials of efavirenz as an Alzheimer's treatment. The HDX data gathered by the National Institute of Standards of Technology (NIST) do support that small doses of efavirenz ramps up the emzyne's cholesterol-removing ability while greater doses inhibit it as it begins to compete with the enzyme for areas on the cholesterol.
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References
"
Shape-Changing Enzyme Suggests How Small Doses of Anti-HIV Drug Might Treat Alzheimer's Disease."
Shape-Changing Enzyme Suggests How Small Doses of Anti-HIV Drug Might Treat Alzheimer's Disease. N.p., n.d. Web. 29 June 2016.
K.W. Anderson, N. Mast, J.W. Hudgens, J.B. Lin, I.V. Turko and I.A. Pikuleva. 2016. Cholesterol Hydroxylase CYP46A1: Mapping of the Allosteric Site for Efavirenz, a Drug that Stimulates Enzyme Activity.
Journal of Biological Chemistry. Published May 27, 2016. DOI:
10.1074/jbc.M116.723577