Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols

@article{citeulike:1581293, abstract = {The structures of F1-ATPase from bovine heart mitochondria inhibited with the dietary phytopolyphenol, resveratrol, and with the related polyphenols quercetin and piceatannol have been determined at 2.3-, 2.4- and 2.7-A resolution, respectively. The inhibitors bind to a common site in the inside surface of an annulus made from loops in the three {alpha}- and three [beta]-subunits beneath the "crown" of [beta]-strands in their N-terminal domains. This region of F1-ATPase forms a bearing to allow the rotation of the tip of the {gamma}-subunit inside the annulus during catalysis. The binding site is a hydrophobic pocket between the C-terminal tip of the {gamma}-subunit and the [beta]TP subunit, and the inhibitors are bound via H-bonds mostly to their hydroxyl moieties mediated by bound water molecules and by hydrophobic interactions. There are no equivalent sites between the {gamma}-subunit and either the [beta]DP or the [beta]E subunit. The inhibitors probably prevent both the synthetic and hydrolytic activities of the enzyme by blocking both senses of rotation of the {gamma}-subunit. The beneficial effects of dietary resveratrol may derive in part by preventing mitochondrial ATP synthesis in tumor cells, thereby inducing apoptosis. 10.1073/pnas.0706290104}, author = {Gledhill, Jonathan R. and Montgomery, Martin G. and Leslie, Andrew G. and Walker, John E. }, citeulike-article-id = {1581293}, doi = {http://dx.doi.org/10.1073/pnas.0706290104}, journal = {PNAS}, keywords = {f1-atpase, inhibitor, motor}, month = {August}, number = {34}, pages = {13632--13637}, posted-at = {2007-08-22 06:29:58}, priority = {2}, title = {Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols}, url = {http://dx.doi.org/10.1073/pnas.0706290104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1581293 L3 - citeulike-article-id:1581293 TI - Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols JF - PNAS VL - 104 IS - 34 SP - 13632 EP - 13637 N2 - The structures of F1-ATPase from bovine heart mitochondria inhibited with the dietary phytopolyphenol, resveratrol, and with the related polyphenols quercetin and piceatannol have been determined at 2.3-, 2.4- and 2.7-A resolution, respectively. The inhibitors bind to a common site in the inside surface of an annulus made from loops in the three {alpha}- and three [beta]-subunits beneath the "crown" of [beta]-strands in their N-terminal domains. This region of F1-ATPase forms a bearing to allow the rotation of the tip of the {gamma}-subunit inside the annulus during catalysis. The binding site is a hydrophobic pocket between the C-terminal tip of the {gamma}-subunit and the [beta]TP subunit, and the inhibitors are bound via H-bonds mostly to their hydroxyl moieties mediated by bound water molecules and by hydrophobic interactions. There are no equivalent sites between the {gamma}-subunit and either the [beta]DP or the [beta]E subunit. The inhibitors probably prevent both the synthetic and hydrolytic activities of the enzyme by blocking both senses of rotation of the {gamma}-subunit. The beneficial effects of dietary resveratrol may derive in part by preventing mitochondrial ATP synthesis in tumor cells, thereby inducing apoptosis. 10.1073/pnas.0706290104 KW - f1-atpase KW - inhibitor KW - motor AU - Gledhill, Jonathan AU - Montgomery, Martin AU - Leslie, Andrew AU - Walker, John PY - 2007/08/21/ UR - http://dx.doi.org/10.1073/pnas.0706290104 ER -