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5x80

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CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS MARR FAMILY PROTEIN RV2887 COMPLEX WITH SALICYLIC ACID

Structural highlights

5x80 is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. This structure supersedes the now removed PDB entry 5hsn. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5x80"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS MARR FAMILY PROTEIN RV2887 COMPLEX WITH SALICYLIC ACID==
-<StructureSection load='5x80' size='340' side='right' caption='[[5x80]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5x80' size='340' side='right'caption='[[5x80]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5x80]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5hsn 5hsn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X80 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5x80]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5hsn 5hsn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X80 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAL:2-HYDROXYBENZOIC+ACID'>SAL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hsn|5hsn]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAL:2-HYDROXYBENZOIC+ACID'>SAL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5x80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x80 OCA], [http://pdbe.org/5x80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x80 RCSB], [http://www.ebi.ac.uk/pdbsum/5x80 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x80 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=5x80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x80 OCA], [https://pdbe.org/5x80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x80 RCSB], [https://www.ebi.ac.uk/pdbsum/5x80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x80 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Bi, L J]]
+[[Category: Large Structures]]
-[[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: P-aminosalicylic acid binding]]
-[[Category: Salicylic acid binding]]
-[[Category: Transcription]]
-[[Category: Whth motif]]

5x80

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS MARR FAMILY PROTEIN RV2887 COMPLEX WITH SALICYLIC ACID

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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