Thanks Alister! On a separate note everyone from my lab was very excited about your talk at the Bay Area meeting on Friday. Hope to be able to tryout ByeLayer soon!

Thanks CJ!

The state dependent binding and positive cooperativeity explain hydrophilic metformin's superior clinical properties and how it is able to effectively inhibit complex I even with low affinity. These results will help facilitate additional therapeutic developments against type 2 #diabetes

We show that hydrophobic biguanides also inhibit complex I in a state dependent manner but their inhibition can be explained using a competitive framework. Whereas, due to the trapping mechanism induced by quinone there is positive cooperativity between the binding of metformin and quinone. 3/n

Our data are consistent with a state-dependent inhibitor trapping mechanism, in which the hydrophilic metformin can only bind to complex I in its "open" state and then gets trapped on the complex due to quinone-binding-induced closing of the active site, trapping metformin in the Q-tunnel. 2/n