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A distal tyrosine residue is required for ligand discrimination in DevS from Mycobacterium tuberculosis
Erik T. Yukl; Alexandra Ioanoviciu; Michiko M. Nakano; Paul R. Ortiz De Montellano; Pierre Moënne-Loccoz(Profiled Authors: Pierre Moenne-Loccoz; Michiko Nakano)
DevS is a heme-based sensor kinase required for sensing environmental conditions leading to nonreplicating persistence in Mycobacterium tuberculosis. Kinase activity is observed when the heme is a ferrous five-coordinate high-spin or six-coordinate low-spin CO or NO complex but is strongly inhibited in the oxy complex. Discrimination between these exogenous ligands has been proposed to depend on a specific hydrogen bond network with bound oxygen. Here we report resonance Raman data and autophosphorylation assays of wild-type and Y171F DevS in various heme complexes. The Y171F mutation eliminates ligand discrimination for CO, NO, and O
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