On the inhibitor effects of bergamot juice flavonoids binding to the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme.
Density functional theory was applied to study the binding mode of new flavonoids as possible inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), an enzyme that catalyzes the four-electron reduction of HMGCoA to mevalonate, the committed step in the biosynthesis of sterols. The investigated flavonoid conjugates brutieridin and melitidin were recently quantified in the bergamot fruit extracts and identified to be structural analogues of statins, lipids concentration lowering drugs that inhibit HMGR. Computations allowed us to perform a detailed analysis of the geometrical and electronic features affecting the binding of these compounds, as well as that of the excellent simvastatin drug, to the active site of the enzyme and to give better insight into the inhibition process.
Leopoldini
Monica
M
Dipartimento di Chimica, Università della Calabria, I-87036 Rende, CS, Italy.
Malaj
Naim
N
Toscano
Marirosa
M
Sindona
Giovanni
G
Russo
Nino
N
D020134:Catalytic Domain; D002957:Citrus / Q000737:chemistry*; D044950:Flavanones / Q000737:chemistry / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism*; D005638:Fruit / Q000737:chemistry*; D006569:Hesperidin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D019821:Simvastatin / Q000378:metabolism
D044950:Flavanones; D005419:Flavonoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C543779:brutieridin; C543780:melitidin; D019821:Simvastatin; D006569:Hesperidin; D006903:Hydroxymethylglutaryl CoA Reductases