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==Crystal Structure of transcriptional regulator Rv1219c of Mycobacterium tuberculosis==
==Crystal Structure of transcriptional regulator Rv1219c of Mycobacterium tuberculosis==
<StructureSection load='4nn1' size='340' side='right' caption='[[4nn1]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
<StructureSection load='4nn1' size='340' side='right'caption='[[4nn1]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4nn1]] is a 1 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=4NN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NN1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4nn1]] is a 1 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=4NN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NN1 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rv1219c, RVBD_1219c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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]] 2.99&#8491;</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=4nn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nn1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nn1 RCSB], [http://www.ebi.ac.uk/pdbsum/4nn1 PDBsum]</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=4nn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nn1 OCA], [https://pdbe.org/4nn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nn1 RCSB], [https://www.ebi.ac.uk/pdbsum/4nn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nn1 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/RAAS_MYCTU RAAS_MYCTU] Regulates the expression of the Rv1217c-Rv1218c multidrug efflux system and its own expression. Acts by binding to promoter regions of Rv1219c and upstream of the Rv1218c gene (PubMed:24424575). Important for survival in prolonged stationary phase and during macrophage infection (PubMed:24590482). May be used to eliminate non-growing mycobacteria (PubMed:25012658).<ref>PMID:24424575</ref> <ref>PMID:24590482</ref> <ref>PMID:25012658</ref>  
The Rv1217c-Rv1218c multidrug efflux system, which belongs to the ATP-binding cassette (ABC) superfamily, recognizes and actively extrudes a variety of structurally unrelated toxic chemicals and mediates the intrinsic resistance to these antimicrobials in Mycobacterium tuberculosis. The expression of Rv1217c-Rv1218c is controlled by the TetR-like transcriptional regulator Rv1219c, which is encoded by a gene immediately upstream of rv1218c. To elucidate the structural basis of Rv1219c regulation, we have determined the crystal structure of Rv1219c, which reveals a dimeric two-domain molecule with an entirely helical architecture similar to members of the TetR family of transcriptional regulators. The N-terminal domains of the Rv1219c dimer are separated by a large center-to-center distance of 64 A. The C-terminal domain of each protomer possesses a large cavity. Docking of small compounds to Rv1219c suggests that this large cavity forms a multidrug binding pocket, which can accommodate a variety of structurally unrelated antimicrobial agents. The internal wall of the multidrug binding site is surrounded by seven aromatic residues, indicating that drug binding may be governed by aromatic stacking interactions. In addition, fluorescence polarization reveals that Rv1219c binds drugs in the micromolar range.
 
Crystal Structure of the transcriptional regulator Rv1219c of Mycobacterium tuberculosis.,Kumar N, Radhakrishnan A, Wright CC, Chou TH, Lei HT, Bolla JR, Tringides ML, Rajashankar KR, Su CC, Purdy GE, Yu EW Protein Sci. 2014 Jan 14. doi: 10.1002/pro.2424. PMID:24424575<ref>PMID:24424575</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Myctu]]
[[Category: Large Structures]]
[[Category: Chou, T H]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Kumar, N]]
[[Category: Chou T-H]]
[[Category: Radhakrishnan, A]]
[[Category: Kumar N]]
[[Category: Yu, E]]
[[Category: Radhakrishnan A]]
[[Category: Dna binding]]
[[Category: Yu E]]
[[Category: Dna binding transcriptional regulator]]
[[Category: Helix turn helix motif]]
[[Category: Transcription]]

Latest revision as of 15:34, 1 March 2024

Crystal Structure of transcriptional regulator Rv1219c of Mycobacterium tuberculosisCrystal Structure of transcriptional regulator Rv1219c of Mycobacterium tuberculosis

Structural highlights

4nn1 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.99Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RAAS_MYCTU Regulates the expression of the Rv1217c-Rv1218c multidrug efflux system and its own expression. Acts by binding to promoter regions of Rv1219c and upstream of the Rv1218c gene (PubMed:24424575). Important for survival in prolonged stationary phase and during macrophage infection (PubMed:24590482). May be used to eliminate non-growing mycobacteria (PubMed:25012658).[1] [2] [3]

References

  1. ↑ Kumar N, Radhakrishnan A, Wright CC, Chou TH, Lei HT, Bolla JR, Tringides ML, Rajashankar KR, Su CC, Purdy GE, Yu EW. Crystal Structure of the transcriptional regulator Rv1219c of Mycobacterium tuberculosis. Protein Sci. 2014 Jan 14. doi: 10.1002/pro.2424. PMID:24424575 doi:http://dx.doi.org/10.1002/pro.2424
  2. ↑ Turapov O, Waddell SJ, Burke B, Glenn S, Sarybaeva AA, Tudo G, Labesse G, Young DI, Young M, Andrew PW, Butcher PD, Cohen-Gonsaud M, Mukamolova GV. Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions. Antimicrob Agents Chemother. 2014 May;58(5):2798-806. doi: 10.1128/AAC.02774-13. , Epub 2014 Mar 3. PMID:24590482 doi:http://dx.doi.org/10.1128/AAC.02774-13
  3. ↑ Turapov O, Waddell SJ, Burke B, Glenn S, Sarybaeva AA, Tudo G, Labesse G, Young DI, Young M, Andrew PW, Butcher PD, Cohen-Gonsaud M, Mukamolova GV. Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria. J Biol Chem. 2014 Sep 5;289(36):25241-9. doi: 10.1074/jbc.M114.577338. Epub 2014 , Jul 10. PMID:25012658 doi:http://dx.doi.org/10.1074/jbc.M114.577338

4nn1, resolution 2.99Å

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