|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='5hso' size='340' side='right'caption='[[5hso]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='5hso' size='340' side='right'caption='[[5hso]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hso]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HSO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HSO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hso]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] and [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=5HSO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HSO FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hsl|5hsl]], [[5hsm|5hsm]], [[5hsn|5hsn]]</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]] 2.5Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hso OCA], [http://pdbe.org/5hso PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hso RCSB], [http://www.ebi.ac.uk/pdbsum/5hso PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hso ProSAT]</span></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=5hso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hso OCA], [https://pdbe.org/5hso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hso RCSB], [https://www.ebi.ac.uk/pdbsum/5hso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hso ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/HTMR_MYCTU HTMR_MYCTU] Represses expression of the HQNO methyltransferase htm gene (Rv0560c) by binding to its promoter region (PubMed:26303802, PubMed:27432954, PubMed:28743871). Also represses the expression of at least five other genes, including the methyltransferase Rv0558 (PubMed:26303802). Binds salicylate (SA), para-aminosalicylic acid (PAS) and gemfibrozil (PubMed:28743871).<ref>PMID:26303802</ref> <ref>PMID:27432954</ref> <ref>PMID:28743871</ref> |
| - | MarR family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. To gain molecular insight into the mechanism of Rv2887, a MarR family protein in M. tuberculosis, we first showed that it binds salicylate (SA) and para-aminosalicylic acid (PAS), its structural analogue and an antitubercular drug, in a 1:1 stoichiometry with high affinity. Subsequent determination and analysis of Rv2887 crystal structures in apo form, and in complex with SA, PAS and DNA showed that SA and PAS bind to Rv2887 at similar sites, and that Rv2887 interacts with DNA mainly by insertion of helix alpha4 into the major groove. Ligand binding triggers rotation of the wHTH domain of Rv2887 toward the dimerization domain, causing changes in protein conformation such that it can no longer bind to a 27 bp recognition sequence in the upstream region of gene Rv0560c. The structures provided here lay a foundation for the design of small molecules that target Rv2887, a potential new approach for the development of anti-mycobacterials.
| + | |
| - | | + | |
| - | Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis.,Gao YR, Li DF, Fleming J, Zhou YF, Liu Y, Deng JY, Zhou L, Zhou J, Zhu GF, Zhang XE, Wang DC, Bi LJ Sci Rep. 2017 Jul 25;7(1):6471. doi: 10.1038/s41598-017-01705-4. PMID:28743871<ref>PMID:28743871</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 5hso" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 21: |
Line 14: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bi, L J]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Gao, Y R]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Li, D F]] | + | [[Category: Bi LJ]] |
| - | [[Category: Wang, D C]] | + | [[Category: Gao YR]] |
| - | [[Category: Dna binding]] | + | [[Category: Li DF]] |
| - | [[Category: Hth-type transcriptional regulator]] | + | [[Category: Wang DC]] |
| - | [[Category: Salicylic acid binding]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
HTMR_MYCTU Represses expression of the HQNO methyltransferase htm gene (Rv0560c) by binding to its promoter region (PubMed:26303802, PubMed:27432954, PubMed:28743871). Also represses the expression of at least five other genes, including the methyltransferase Rv0558 (PubMed:26303802). Binds salicylate (SA), para-aminosalicylic acid (PAS) and gemfibrozil (PubMed:28743871).[1] [2] [3]
References
- ↑ Winglee K, Lun S, Pieroni M, Kozikowski A, Bishai W. Mutation of Rv2887, a marR-like gene, confers Mycobacterium tuberculosis resistance to an imidazopyridine-based agent. Antimicrob Agents Chemother. 2015 Nov;59(11):6873-81. PMID:26303802 doi:10.1128/AAC.01341-15
- ↑ Warrier T, Kapilashrami K, Argyrou A, Ioerger TR, Little D, Murphy KC, Nandakumar M, Park S, Gold B, Mi J, Zhang T, Meiler E, Rees M, Somersan-Karakaya S, Porras-De Francisco E, Martinez-Hoyos M, Burns-Huang K, Roberts J, Ling Y, Rhee KY, Mendoza-Losana A, Luo M, Nathan CF. N-methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4523-30. doi:, 10.1073/pnas.1606590113. Epub 2016 Jul 18. PMID:27432954 doi:http://dx.doi.org/10.1073/pnas.1606590113
- ↑ Gao YR, Li DF, Fleming J, Zhou YF, Liu Y, Deng JY, Zhou L, Zhou J, Zhu GF, Zhang XE, Wang DC, Bi LJ. Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis. Sci Rep. 2017 Jul 25;7(1):6471. doi: 10.1038/s41598-017-01705-4. PMID:28743871 doi:http://dx.doi.org/10.1038/s41598-017-01705-4
|
