Myxopyronin: a punch in the jaws of bacterial RNA polymerase

Abstract

Evaluation of: Belogurov GA, Vassylyeva MN, Sevostyanova A et  al.: Transcription inactivation through local refolding of the RNA polymerase structure. Nature 457, 332–335 (2008) and, Mukhopadhyay J, Das K, Ismail S et  al.: The RNA polymerase ‘switch region’ is a target for inhibitors. Cell 135, 295–307 (2008). Bacterial RNA polymerase is an essential enzyme, which is responsible for synthesizing RNA from a DNA template and is targeted by a number of antibiotics. The mechanism of action of two closely related transcription inhibitors, myxopyronin B and a synthetic analog desmethyl-myxopyronin was elucidated, together with the structures of the antibiotic–RNA polymerase complexes. The studies reveal a new binding site and a new mechanism of action affecting the jaw domain of the enzyme. As the need for new antibiotics increase, these studies open new ways to the synthesis of more potent myxopyronin analogs.