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| | ==Crystal structure of the effector-binding domain of DasR (DasR-EBD) in complex with glucosamine-6-phosphate== | | ==Crystal structure of the effector-binding domain of DasR (DasR-EBD) in complex with glucosamine-6-phosphate== |
| - | <StructureSection load='4zsi' size='340' side='right' caption='[[4zsi]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='4zsi' size='340' side='right'caption='[[4zsi]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zsi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZSI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zsi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor_A3(2) Streptomyces coelicolor A3(2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4R1:BETA-GLUCOSAMINE-6-PHOSPHATE'>4R1</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLP:GLUCOSAMINE+6-PHOSPHATE'>GLP</scene></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]] 1.652Å</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=4zsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsi OCA], [http://pdbe.org/4zsi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zsi RCSB], [http://www.ebi.ac.uk/pdbsum/4zsi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsi ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4R1:BETA-GLUCOSAMINE-6-PHOSPHATE'>4R1</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLP:GLUCOSAMINE+6-PHOSPHATE'>GLP</scene></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=4zsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsi OCA], [https://pdbe.org/4zsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsi RCSB], [https://www.ebi.ac.uk/pdbsum/4zsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DASR_STRCO DASR_STRCO]] Global regulator that is part of the nutrient-sensing system. In the absence of N-acetylglucosamine 6-P, represses the phosphotransferase system (PTS) specific for the uptake of N-acetylglucosamine (PTSNag), and genes involved in the metabolism of chitin, as well as several genes involved in development, thereby linking carbon availability to morphogenesis. Binds to the DNA consensus sequence 5'-ACTGGTCTAGACCACT-3'.<ref>PMID:15247334</ref> <ref>PMID:16925557</ref> | + | [https://www.uniprot.org/uniprot/DASR_STRCO DASR_STRCO] Global regulator that is part of the nutrient-sensing system. In the absence of N-acetylglucosamine 6-P, represses the phosphotransferase system (PTS) specific for the uptake of N-acetylglucosamine (PTSNag), and genes involved in the metabolism of chitin, as well as several genes involved in development, thereby linking carbon availability to morphogenesis. Binds to the DNA consensus sequence 5'-ACTGGTCTAGACCACT-3'.<ref>PMID:15247334</ref> <ref>PMID:16925557</ref> |
| | <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: Fillenberg, S B]] | + | [[Category: Large Structures]] |
| - | [[Category: Koerner, S]] | + | [[Category: Fillenberg SB]] |
| - | [[Category: Muller, Y A]] | + | [[Category: Koerner S]] |
| - | [[Category: Bacterial transcription regulation]] | + | [[Category: Muller YA]] |
| - | [[Category: Effector-binding domain]]
| + | |
| - | [[Category: Glucosamine-6-phosphate]]
| + | |
| - | [[Category: Gntr/hutc family]]
| + | |
| - | [[Category: Master regulator]]
| + | |
| - | [[Category: N-acetylglucosamine utilization]]
| + | |
| - | [[Category: Repressor]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Function
DASR_STRCO Global regulator that is part of the nutrient-sensing system. In the absence of N-acetylglucosamine 6-P, represses the phosphotransferase system (PTS) specific for the uptake of N-acetylglucosamine (PTSNag), and genes involved in the metabolism of chitin, as well as several genes involved in development, thereby linking carbon availability to morphogenesis. Binds to the DNA consensus sequence 5'-ACTGGTCTAGACCACT-3'.[1] [2]
Publication Abstract from PubMed
Small molecule effectors regulate gene transcription in bacteria by altering the DNA-binding affinities of specific repressor proteins. Although the GntR proteins represent a large family of bacterial repressors, only little is known about the allosteric mechanism that enables their function. DasR from Streptomyces coelicolor belongs to the GntR/HutC subfamily and specifically recognises operators termed DasR-responsive elements (dre-sites). Its DNA-binding properties are modulated by phosphorylated sugars. Here, we present several crystal structures of DasR, namely of dimeric full-length DasR in the absence of any effector and of only the effector-binding domain (EBD) of DasR without effector or in complex with glucosamine-6-phosphate (GlcN-6-P) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P). Together with molecular dynamics (MD) simulations and a comparison with other GntR/HutC family members these data allowed for a structural characterisation of the different functional states of DasR. Allostery in DasR and possibly in many other GntR/HutC family members is best described by a conformational selection model. In ligand-free DasR, an increased flexibility in the EBDs enables the attached DNA-binding domains (DBD) to sample a variety of different orientations and among these also a DNA-binding competent conformation. Effector binding to the EBDs of DasR significantly reorganises the atomic structure of the latter. However, rather than locking the orientation of the DBDs, the effector-induced formation of beta-strand beta* in the DBD-EBD-linker segment merely appears to take the DBDs 'on a shorter leash' thereby impeding the 'downwards' positioning of the DBDs that is necessary for a concerted binding of two DBDs of DasR to operator DNA.
Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors.,Fillenberg SB, Friess MD, Korner S, Bockmann RA, Muller YA PLoS One. 2016 Jun 23;11(6):e0157691. doi: 10.1371/journal.pone.0157691., eCollection 2016. PMID:27337024[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rigali S, Schlicht M, Hoskisson P, Nothaft H, Merzbacher M, Joris B, Titgemeyer F. Extending the classification of bacterial transcription factors beyond the helix-turn-helix motif as an alternative approach to discover new cis/trans relationships. Nucleic Acids Res. 2004 Jun 24;32(11):3418-26. Print 2004. PMID:15247334 doi:http://dx.doi.org/10.1093/nar/gkh673
- ↑ Rigali S, Nothaft H, Noens EE, Schlicht M, Colson S, Muller M, Joris B, Koerten HK, Hopwood DA, Titgemeyer F, van Wezel GP. The sugar phosphotransferase system of Streptomyces coelicolor is regulated by the GntR-family regulator DasR and links N-acetylglucosamine metabolism to the control of development. Mol Microbiol. 2006 Sep;61(5):1237-51. PMID:16925557 doi:http://dx.doi.org/MMI5319
- ↑ Fillenberg SB, Friess MD, Korner S, Bockmann RA, Muller YA. Crystal Structures of the Global Regulator DasR from Streptomyces coelicolor: Implications for the Allosteric Regulation of GntR/HutC Repressors. PLoS One. 2016 Jun 23;11(6):e0157691. doi: 10.1371/journal.pone.0157691., eCollection 2016. PMID:27337024 doi:http://dx.doi.org/10.1371/journal.pone.0157691
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