Inhibition of the Fe4S4-Cluster-Containing Protein IspH (LytB): Electron Paramagnetic Resonance, Metallacycles, and Mechanisms

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Inhibition of the Fe(4)S(4)-cluster-containing protein IspH (LytB): electron paramagnetic resonance, metallacycles, and mechanisms.

We report the inhibition of the Aquifex aeolicus IspH enzyme (LytB, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, EC 1.17.1.2) by a series of diphosphates and bisphosphonates. The most active species was an alkynyl diphosphate having IC(50) = 0.45 microM (K(i) approximately 60 nM), which generated a very large change in the 9 GHz EPR spectrum of the reduced protein. On the basis of p...

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ژورنال

عنوان ژورنال: Journal of the American Chemical Society

سال: 2010

ISSN: 0002-7863,1520-5126

DOI: 10.1021/ja909664j