7ve5: Difference between revisions
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==== | ==C-terminal domain of VraR== | ||
<StructureSection load='7ve5' size='340' side='right'caption='[[7ve5]]' scene=''> | <StructureSection load='7ve5' size='340' side='right'caption='[[7ve5]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ve5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VE5 FirstGlance]. <br> | ||
</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=7ve5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ve5 OCA], [https://pdbe.org/7ve5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ve5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ve5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ve5 ProSAT]</span></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]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7ve5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ve5 OCA], [https://pdbe.org/7ve5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ve5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ve5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ve5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/VRAR_STAA8 VRAR_STAA8] Member of the two-component regulatory system VraS/VraR involved in the control of the cell wall peptidoglycan biosynthesis. Upon cellular stress, the histidine kinase VraS transfers the phosphoryl group onto VraR. Upon phosphorylation, VraR dimerizes at the N-terminal domain. In turn, phosphorylation-induced dimerization expand and enhance the VraR binding to its own promoter leading to increased expression and subsequent modulation of as many as 40 genes, which ultimately constitute the S.aureus response to cell wall damage (PubMed:31277575). In addition, inhibits the host autophagic flux and delays the early stage of autophagosome formation, thereby promoting bacterial survival. Facilitates the ability of S.aureus to resist host polymorphonuclear leukocytes-mediated phagocytosis and killing thus contributing to immune evasion (By similarity).[UniProtKB:Q9KWK8]<ref>PMID:31277575</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In Staphylococcus aureus, vancomycin-resistance-associated response regulator (VraR) is a part of the VraSR two-component system, which is responsible for activating a cell wall-stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR-binding sites have been identified: R1 and R2 in the vraSR operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N-terminal receiver domain (VraRN ) connected to a C-terminal DNA binding domain (VraRC ) with a flexible linker. Here, we present the crystal structure of VraRC alone and in complex with R1-DNA in 1.87- and 2.0-A resolution, respectively. VraRC consisting of four alpha-helices forms a dimer when interacting with R1-DNA. In the VraRC -DNA complex structure, Mg(2+) ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg(2+) to VraRC enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraRC with R1- and R2-DNA revealed the essential residues that might play a crucial role in interacting with DNA of the vraSR operon. The structural information could help in designing and screening potential therapeutics/inhibitors to deal with antibiotic-resistant S. aureus via targeting VraR. | |||
Structural insights into DNA binding domain of vancomycin-resistance-associated response regulator in complex with its promoter DNA from Staphylococcus aureus.,Kumar JV, Tseng TS, Lou YC, Wei SY, Wu TH, Tang HC, Chiu YC, Hsu CH, Chen C Protein Sci. 2022 May;31(5):e4286. doi: 10.1002/pro.4286. PMID:35481641<ref>PMID:35481641</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ve5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Response regulator 3D structure|Response regulator 3D structure]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Staphylococcus aureus]] | ||
[[Category: Staphylococcus aureus subsp. aureus Mu50]] | |||
[[Category: Chen C]] | |||
[[Category: Hsu CH]] | |||
[[Category: Kumar JV]] | |||
Latest revision as of 20:23, 29 November 2023
C-terminal domain of VraRC-terminal domain of VraR
Structural highlights
FunctionVRAR_STAA8 Member of the two-component regulatory system VraS/VraR involved in the control of the cell wall peptidoglycan biosynthesis. Upon cellular stress, the histidine kinase VraS transfers the phosphoryl group onto VraR. Upon phosphorylation, VraR dimerizes at the N-terminal domain. In turn, phosphorylation-induced dimerization expand and enhance the VraR binding to its own promoter leading to increased expression and subsequent modulation of as many as 40 genes, which ultimately constitute the S.aureus response to cell wall damage (PubMed:31277575). In addition, inhibits the host autophagic flux and delays the early stage of autophagosome formation, thereby promoting bacterial survival. Facilitates the ability of S.aureus to resist host polymorphonuclear leukocytes-mediated phagocytosis and killing thus contributing to immune evasion (By similarity).[UniProtKB:Q9KWK8][1] Publication Abstract from PubMedIn Staphylococcus aureus, vancomycin-resistance-associated response regulator (VraR) is a part of the VraSR two-component system, which is responsible for activating a cell wall-stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR-binding sites have been identified: R1 and R2 in the vraSR operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N-terminal receiver domain (VraRN ) connected to a C-terminal DNA binding domain (VraRC ) with a flexible linker. Here, we present the crystal structure of VraRC alone and in complex with R1-DNA in 1.87- and 2.0-A resolution, respectively. VraRC consisting of four alpha-helices forms a dimer when interacting with R1-DNA. In the VraRC -DNA complex structure, Mg(2+) ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg(2+) to VraRC enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraRC with R1- and R2-DNA revealed the essential residues that might play a crucial role in interacting with DNA of the vraSR operon. The structural information could help in designing and screening potential therapeutics/inhibitors to deal with antibiotic-resistant S. aureus via targeting VraR. Structural insights into DNA binding domain of vancomycin-resistance-associated response regulator in complex with its promoter DNA from Staphylococcus aureus.,Kumar JV, Tseng TS, Lou YC, Wei SY, Wu TH, Tang HC, Chiu YC, Hsu CH, Chen C Protein Sci. 2022 May;31(5):e4286. doi: 10.1002/pro.4286. PMID:35481641[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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