5lcy

Formaldehyde-Responsive Regulator FrmR E64H variant from Salmonella enterica serovar Typhimurium

spinqualitylabelsall models 5lcy, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lcy is a 4 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.19Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0H3NLH8_SALTS Publication Abstract from PubMed The DUF156 family of DNA-binding, transcriptional-regulators include metal-sensors which respond to cobalt and/or nickel (RcnR, InrS) or copper (CsoR), plus CstR which responds to persulfide, and formaldehyde-responsive FrmR. Unexpectedly, the allosteric mechanism of FrmR from Salmonella enterica serovar Typhimurium is triggered by metals in vitro and variant FrmRE64H gains responsiveness to Zn(II) and cobalt in vivo Here we establish that the allosteric mechanism of FrmR is triggered directly by formaldehyde in vitro Sensitivity to formaldehyde requires a cysteine (Cys35 in FrmR) conserved in all DUF156 proteins. A crystal structure of metal- and formaldehyde-sensing FrmRE64H reveals that an FrmR-specific amino-terminal Pro2 is proximal to Cys35 and these residues form the deduced formaldehyde-sensing site. Evidence is presented which implies that residues spatially close to the conserved cysteine tune the sensitivities of DUF156 proteins above or below critical thresholds for different effectors, generating the semblance of specificity within cells. Relative to FrmR, RcnR is less responsive to formaldehyde in vitro and RcnR does not sense formaldehyde in vivo, but reciprocal mutations FrmRP2S and RcnRS2P respectively impair or enhance formaldehyde-reactivity in vitro Formaldehyde-detoxification by FrmA requires S-(hydroxymethyl)glutathione, yet glutathione inhibits formaldehyde detection by FrmR in vivo and in vitro Quantifying the number of FrmR molecules per cell and modelling formaldehyde modification as a function of [formaldehyde], demonstrates that FrmR-reactivity is optimised such that FrmR is modified, and frmRA de-repressed, at lower [formaldehyde] than required to generate S-(hydroxymethyl)glutathione. Expression of FrmA is thereby coordinated with the accumulation of its substrate. The Effectors and Sensory Sites of Formaldehyde-Responsive Regulator FrmR and Metal-Sensing Variant.,Osman D, Piergentili C, Chen J, Sayer LN, Uson I, Huggins TG, Robinson NJ, Pohl E J Biol Chem. 2016 Jul 29. pii: jbc.M116.745174. PMID:27474740 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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