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| | ==Formaldehyde-Responsive Regulator FrmR E64H variant from Salmonella enterica serovar Typhimurium== | | ==Formaldehyde-Responsive Regulator FrmR E64H variant from Salmonella enterica serovar Typhimurium== |
| - | <StructureSection load='5lcy' size='340' side='right' caption='[[5lcy]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='5lcy' size='340' side='right'caption='[[5lcy]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lcy]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LCY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LCY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lcy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium Salmonella enterica subsp. enterica serovar Typhimurium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LCY FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lcy OCA], [http://pdbe.org/5lcy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lcy RCSB], [http://www.ebi.ac.uk/pdbsum/5lcy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lcy ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.19Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5lcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lcy OCA], [https://pdbe.org/5lcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lcy RCSB], [https://www.ebi.ac.uk/pdbsum/5lcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lcy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0H3NLH8_SALTS A0A0H3NLH8_SALTS] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Osman, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Piergentili, C]] | + | [[Category: Salmonella enterica subsp. enterica serovar Typhimurium]] |
| - | [[Category: Pohl, E]] | + | [[Category: Osman D]] |
| - | [[Category: Robinson, N]] | + | [[Category: Piergentili C]] |
| - | [[Category: Uson, I]] | + | [[Category: Pohl E]] |
| - | [[Category: Formaldehyde]] | + | [[Category: Robinson N]] |
| - | [[Category: Frmr]] | + | [[Category: Uson I]] |
| - | [[Category: Rcnr]]
| + | |
| - | [[Category: Salmonella enterica]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Zinc]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Osman D, Piergentili C, Chen J, Sayer LN, Uson I, Huggins TG, Robinson NJ, Pohl E. The Effectors and Sensory Sites of Formaldehyde-Responsive Regulator FrmR and Metal-Sensing Variant. J Biol Chem. 2016 Jul 29. pii: jbc.M116.745174. PMID:27474740 doi:http://dx.doi.org/10.1074/jbc.M116.745174
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