3cgz
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Revision as of 08:33, 14 May 2008
Crystal Structure of Salmonella Sensor Kinase PhoQ catalytic domain
Overview
Sensor kinases in the bacterial two-component system share a unique ATP-binding Bergerat fold with the GHL (gyrase, Hsp90, and MutL) family of proteins. We demonstrated that selected GHL inhibitors bind to the catalytic domain of sensor kinase PhoQ (PhoQcat) using NMR chemical shift perturbation experiments. Using crystallographic approaches, we show that radicicol (an Hsp90 inhibitor) binds and interacts specifically with residues in the ATP-binding pocket of PhoQ. The interaction between radicicol and PhoQcat demonstrates significant similarities as well as differences compared to AMPPNP (a non-hydrolyzable ATP analog) bound to PhoQcat and radicicol bound to Hsp90. Our results suggest that GHL inhibitors may be useful lead compounds for developing sensor kinase inhibitors.
About this Structure
3CGZ is a Single protein structure of sequence from Salmonella typhimurium. Full crystallographic information is available from OCA.
Reference
The Hsp90 inhibitor radicicol interacts with the ATP-binding pocket of bacterial sensor kinase PhoQ., Guarnieri MT, Zhang L, Shen J, Zhao R, J Mol Biol. 2008 May 23;379(1):82-93. Epub 2008 Mar 26. PMID:18440021 Page seeded by OCA on Wed May 14 11:33:29 2008
Categories: Histidine kinase | Salmonella typhimurium | Single protein | Guarnieri, M T. | Shen, J. | Zhang, L. | Zhao, R. | Alpha-beta sandwich | Atp-binding | Bergerat fold | Growth regulation | Inner membrane | Kinase | Magnesium | Membrane | Metal-binding | Nucleotide-binding | Phosphoprotein | Transferase | Transmembrane | Two-component regulatory system | Virulence
