A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL

E Chapman, GW Farr, K Furtak, AL Horwich

Index: Chapman, Eli; Farr, George W.; Furtak, Krystyna; Horwich, Arthur L. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 3 p. 811 - 813

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Citation Number: 9

Abstract

The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed ...