title: On the inhibitor effects of bergamot juice flavonoids binding to the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme.
abstract: 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.
authors.affiliation: Dipartimento di Chimica, Università della Calabria, I-87036 Rende, CS, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Leopoldini
authors.forename: Naim
authors.initials: N
authors.lastname: Malaj
authors.forename: Marirosa
authors.initials: M
authors.lastname: Toscano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sindona
authors.forename: Nino
authors.initials: N
authors.lastname: Russo
mesh_terms: 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
chemical_list: D044950:Flavanones; D005419:Flavonoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C543779:brutieridin; C543780:melitidin; D019821:Simvastatin; D006569:Hesperidin; D006903:Hydroxymethylglutaryl CoA Reductases