3cgz
From Proteopedia
Crystal Structure of Salmonella Sensor Kinase PhoQ catalytic domain
Structural highlights
Function[PHOQ_SALTY] Member of the two-component regulatory system PhoP/PhoQ which regulates the expression of genes involved in virulence, adaptation to acidic and low Mg(2+) environments and resistance to host defense antimicrobial peptides. Essential for intramacrophage survival of S.typhimurium. In low periplasmic Mg(2+), PhoQ functions as a membrane-associated protein kinase that undergoes autophosphorylation and subsequently transfers the phosphate to PhoP, resulting in the expression of PhoP-activated genes (PAG) and repression of PhoP-repressed genes (PRG). In high periplasmic Mg(2+), acts as a protein phosphatase that dephosphorylates phospho-PhoP, resulting in the repression of PAG and may lead to expression of some PRG. Essential for transcription of spiC inside macrophages by controlling the expression of the two-component regulatory system SsrB/SpiR (SsrA) and Pir at transcriptional and post-transcriptional levels respectively. Promotes expression of the two-component regulatory system PmrA/PmrB via activation of pmrD gene. Is required to attenuate bacterial growth within fibroblast cells and to enhance bacterial resistance to bile in intestinal cells. Negatively regulates prgH, which is required for invasion of epithelial cells. Involved in acid tolerance.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSensor 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. 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Histidine kinase | 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
