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Published August 26, 2005 | Published
Journal Article Open

Structural and chemical requirements for histidine phosphorylation by the chemotaxis kinase CheA


The CheA histidine kinase initiates the signal transduction pathway of bacterial chemotaxis by autophosphorylating a conserved histidine on its phosphotransferase domain (P1). Site-directed mutations of neighboring conserved P1 residues (Glu-67, Lys-48, and His-64) show that a hydrogen-bonding network controls the reactivity of the phospho-accepting His (His-45) in Thermotoga maritima CheA. In particular, the conservative mutation E67Q dramatically reduces phospho-transfer to P1 without significantly affecting the affinity of P1 for the CheA ATP-binding domain. High resolution crystallographic studies revealed that although all mutants disrupt the hydrogen-bonding network to varying degrees, none affect the conformation of His-45. N-15-NMR chemical shift studies instead showed that Glu-67 functions to stabilize the unfavored (NH)-H-delta 1 tautomer of His-45, thereby rendering the N-epsilon 2 imidazole unprotonated and well positioned for accepting the ATP phosphoryl group.

Additional Information

© 2005 the American Society for Biochemistry and Molecular Biology. Received for publication, May 16, 2005, and in revised form, June 24, 2005. We thank the Cornell High Energy Synchrotron (CHESS) for access to data collection facilities. This work was supported by National Institutes of Health Grants R01-AI 19296 (to M.I.S.), 5R01GM059544-25 (to F.W.D.), and R01-GM066775 (to B.R.C.), an National Institutes of Health predoctoral fellowship (to C.M.Q.), and a Cornell Presidential Research Scholars stipend (to C.G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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