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| | <StructureSection load='6cyy' size='340' side='right'caption='[[6cyy]], [[Resolution|resolution]] 2.51Å' scene=''> | | <StructureSection load='6cyy' size='340' side='right'caption='[[6cyy]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cyy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CYY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CYY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cyy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CYY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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]] 2.506Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6cz6|6cz6]], [[6cyj|6cyj]], [[6d2s|6d2s]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">prpR, Rv1129c, RVBD_1129c, P425_01178 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6cyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cyy OCA], [https://pdbe.org/6cyy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cyy RCSB], [https://www.ebi.ac.uk/pdbsum/6cyy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cyy ProSAT]</span></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=6cyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cyy OCA], [http://pdbe.org/6cyy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cyy RCSB], [http://www.ebi.ac.uk/pdbsum/6cyy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cyy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRPR_MYCTU PRPR_MYCTU]] Plays a key role in regulating expression of enzymes involved in the catabolism of short chain fatty acids (SCFA) via both the glyoxylate (acetyl degradation route) and the methylcitrate cycle (propionate degradation route) (PubMed:22916289, PubMed:24705740). Required for intracellular growth in macrophages and for the assimilation of cholesterol-derived propionate (PubMed:22365605). PrpR acts as a transcriptional activator of prpDC and icl genes when propionate is the main carbon source, and as a ramB repressor (PubMed:22916289). During growth on propionate, PrpR also acts as a transcriptional repressor of dnaA, which encodes the DnaA initiator protein responsible for initiating chromosomal replication (PubMed:24705740). It is possibly involved in the regulation of genes responsible for controlling cholesterol utilization (PubMed:22365605).<ref>PMID:22365605</ref> <ref>PMID:22916289</ref> <ref>PMID:24705740</ref> | + | [https://www.uniprot.org/uniprot/PRPR_MYCTU PRPR_MYCTU] Plays a key role in regulating expression of enzymes involved in the catabolism of short chain fatty acids (SCFA) via both the glyoxylate (acetyl degradation route) and the methylcitrate cycle (propionate degradation route) (PubMed:22916289, PubMed:24705740). Required for intracellular growth in macrophages and for the assimilation of cholesterol-derived propionate (PubMed:22365605). PrpR acts as a transcriptional activator of prpDC and icl genes when propionate is the main carbon source, and as a ramB repressor (PubMed:22916289). During growth on propionate, PrpR also acts as a transcriptional repressor of dnaA, which encodes the DnaA initiator protein responsible for initiating chromosomal replication (PubMed:24705740). It is possibly involved in the regulation of genes responsible for controlling cholesterol utilization (PubMed:22365605).<ref>PMID:22365605</ref> <ref>PMID:22916289</ref> <ref>PMID:24705740</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6cyy" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6cyy" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Sacchettini, J]] | + | [[Category: Sacchettini J]] |
| - | [[Category: Tang, S]] | + | [[Category: Tang S]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Regulator]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
PRPR_MYCTU Plays a key role in regulating expression of enzymes involved in the catabolism of short chain fatty acids (SCFA) via both the glyoxylate (acetyl degradation route) and the methylcitrate cycle (propionate degradation route) (PubMed:22916289, PubMed:24705740). Required for intracellular growth in macrophages and for the assimilation of cholesterol-derived propionate (PubMed:22365605). PrpR acts as a transcriptional activator of prpDC and icl genes when propionate is the main carbon source, and as a ramB repressor (PubMed:22916289). During growth on propionate, PrpR also acts as a transcriptional repressor of dnaA, which encodes the DnaA initiator protein responsible for initiating chromosomal replication (PubMed:24705740). It is possibly involved in the regulation of genes responsible for controlling cholesterol utilization (PubMed:22365605).[1] [2] [3]
Publication Abstract from PubMed
The pathogenicity of Mycobacterium tuberculosis depends upon its ability to catabolize host cholesterol. Upregulation of the methylcitrate cycle (MCC) is required to assimilate and detoxify propionyl-CoA, a cholesterol degradation product. The transcription of key genes prpC and prpD in MCC is activated by MtPrpR, a member of a family of prokaryotic transcription factors whose structures and modes of action have not been clearly defined. We show that MtPrpR has a novel overall structure and directly binds to CoA or short-chain acyl-CoA derivatives to form a homotetramer that covers the binding cavity and locks CoA tightly inside the protein. The regulation of this process involves a [4Fe4S] cluster located close to the CoA-binding cavity on a neighboring chain. Mutations in the [4Fe4S] cluster binding residues rendered MtPrpR incapable of regulating MCC gene transcription. The structure of MtPrpR without the [4Fe4S] cluster-binding region shows a conformational change that prohibits CoA binding. The stability of this cluster means it is unlikely a redox sensor but may function by sensing ambient iron levels. These results provide mechanistic insights into this family of critical transcription factors who share similar structures and regulate gene transcription using a combination of acyl-CoAs and [4Fe4S] cluster.
Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor.,Tang S, Hicks ND, Cheng YS, Silva A, Fortune SM, Sacchettini JC Nucleic Acids Res. 2019 Oct 10;47(18):9934-9949. doi: 10.1093/nar/gkz724. PMID:31504787[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Griffin JE, Pandey AK, Gilmore SA, Mizrahi V, McKinney JD, Bertozzi CR, Sassetti CM. Cholesterol catabolism by Mycobacterium tuberculosis requires transcriptional and metabolic adaptations. Chem Biol. 2012 Feb 24;19(2):218-27. doi: 10.1016/j.chembiol.2011.12.016. PMID:22365605 doi:http://dx.doi.org/10.1016/j.chembiol.2011.12.016
- ↑ Masiewicz P, Brzostek A, Wolanski M, Dziadek J, Zakrzewska-Czerwinska J. A novel role of the PrpR as a transcription factor involved in the regulation of methylcitrate pathway in Mycobacterium tuberculosis. PLoS One. 2012;7(8):e43651. doi: 10.1371/journal.pone.0043651. Epub 2012 Aug 16. PMID:22916289 doi:http://dx.doi.org/10.1371/journal.pone.0043651
- ↑ Masiewicz P, Wolanski M, Brzostek A, Dziadek J, Zakrzewska-Czerwinska J. Propionate represses the dnaA gene via the methylcitrate pathway-regulating transcription factor, PrpR, in Mycobacterium tuberculosis. Antonie Van Leeuwenhoek. 2014 May;105(5):951-9. doi: 10.1007/s10482-014-0153-0., Epub 2014 Apr 5. PMID:24705740 doi:http://dx.doi.org/10.1007/s10482-014-0153-0
- ↑ Tang S, Hicks ND, Cheng YS, Silva A, Fortune SM, Sacchettini JC. Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor. Nucleic Acids Res. 2019 Oct 10;47(18):9934-9949. doi: 10.1093/nar/gkz724. PMID:31504787 doi:http://dx.doi.org/10.1093/nar/gkz724
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