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| | <StructureSection load='5is1' size='340' side='right'caption='[[5is1]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5is1' size='340' side='right'caption='[[5is1]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5is1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IS1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IS1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5is1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IS1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IS1 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">walK, walK_1, AL493_01420, AL498_11610, AL508_14645, AM595_00105, ASU36_11995, AUC48_00105, AUC49_00105, AUC50_00105, BN1321_430109, CH51_00105, EQ80_000105, ER12_000105, ERS092844_02460, ERS093009_00906, ERS179246_01836, ERS195423_01765, ERS365775_01678, ERS410449_00558, ERS411009_01438, ERS411017_01103, ERS445051_00023, ERS445052_00659, FE68_05490, NI36_00110, RL02_04070, RT87_00105, SA7112_13655, SASCBU26_00023 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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]] 1.998Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histidine_kinase Histidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.13.3 2.7.13.3] </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=5is1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5is1 OCA], [https://pdbe.org/5is1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5is1 RCSB], [https://www.ebi.ac.uk/pdbsum/5is1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5is1 ProSAT]</span></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=5is1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5is1 OCA], [http://pdbe.org/5is1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5is1 RCSB], [http://www.ebi.ac.uk/pdbsum/5is1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5is1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/WALK_STAA8 WALK_STAA8] Member of the two-component regulatory system WalK/WalR that regulates genes involved in cell wall metabolism, virulence regulation, biofilm production, oxidative stress resistance and antibiotic resistance via direct or indirect regulation of autolysins (PubMed:14762013, PubMed:17827301, PubMed:22825451). Functions as a sensor protein kinase which is autophosphorylated at a histidine residue in the dimerization domain and transfers its phosphate group to the conserved aspartic acid residue in the regulatory domain of WalR. In turn, WalR binds to the upstream promoter regions of the target genes to positively and negatively regulate their expression (PubMed:14762013, PubMed:22825451).<ref>PMID:14762013</ref> <ref>PMID:17827301</ref> <ref>PMID:22825451</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histidine kinase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Choi, J]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Kim, K K]] | + | [[Category: Choi J]] |
| - | [[Category: Kim, T]] | + | [[Category: Kim KK]] |
| - | [[Category: Lee, S]] | + | [[Category: Kim T]] |
| - | [[Category: Membrane protein]] | + | [[Category: Lee S]] |
| - | [[Category: Nest motif]]
| + | |
| - | [[Category: Pas/pdc domain]]
| + | |
| - | [[Category: Sensor histidine kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
WALK_STAA8 Member of the two-component regulatory system WalK/WalR that regulates genes involved in cell wall metabolism, virulence regulation, biofilm production, oxidative stress resistance and antibiotic resistance via direct or indirect regulation of autolysins (PubMed:14762013, PubMed:17827301, PubMed:22825451). Functions as a sensor protein kinase which is autophosphorylated at a histidine residue in the dimerization domain and transfers its phosphate group to the conserved aspartic acid residue in the regulatory domain of WalR. In turn, WalR binds to the upstream promoter regions of the target genes to positively and negatively regulate their expression (PubMed:14762013, PubMed:22825451).[1] [2] [3]
Publication Abstract from PubMed
Bacterial two-component signal transduction systems are used to adapt to fluctuations in the environment. YycG, a key two-component histidine kinase in Staphylococcus aureus, plays an essential role in cell viability and regulates cell wall metabolism, biofilm formation, virulence, and antibiotic resistance. For these reasons, YycG is considered a compelling target for the development of novel antibiotics. However, to date, the signaling mechanism of YycG and its stimulus are poorly understood mainly because of a lack of structural information on YycG. To address this deficiency, we determined the crystal structure of the extracellular domain of S. aureus YycG (YycGex) at 2.0-A resolution. The crystal structure indicated two subunits with an extracellular Per-Arnt-Sim (PAS) topology packed into a dimer with interloop interactions. Disulfide scanning using cysteine-substituted mutants revealed that YycGex possessed dimeric interfaces not only in the loop but also in the helix alpha1. Cross-linking studies using intact YycG demonstrated that it was capable of forming high molecular weight oligomers on the cell membrane. Furthermore, we also observed that two auxiliary proteins of YycG, YycH and YycI, cooperatively interfered with the multimerization of YycG. From these results, we propose that signaling through YycG is regulated by multimerization and binding of YycH and YycI. These structural studies, combined with biochemical analyses, provide a better understanding of the signaling mechanism of YycG, which is necessary for developing novel antibacterial drugs targeting S. aureus.
Structural Studies on the Extracellular Domain of Sensor Histidine Kinase YycG from Staphylococcus aureus and Its Functional Implications.,Kim T, Choi J, Lee S, Yeo KJ, Cheong HK, Kim KK J Mol Biol. 2016 Jul 4. pii: S0022-2836(16)30241-8. doi:, 10.1016/j.jmb.2016.06.019. PMID:27389096[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dubrac S, Msadek T. Identification of genes controlled by the essential YycG/YycF two-component system of Staphylococcus aureus. J Bacteriol. 2004 Feb;186(4):1175-81. PMID:14762013 doi:10.1128/JB.186.4.1175-1181.2004
- ↑ Dubrac S, Boneca IG, Poupel O, Msadek T. New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. J Bacteriol. 2007 Nov;189(22):8257-69. PMID:17827301 doi:10.1128/JB.00645-07
- ↑ Delauné A, Dubrac S, Blanchet C, Poupel O, Mäder U, Hiron A, Leduc A, Fitting C, Nicolas P, Cavaillon JM, Adib-Conquy M, Msadek T. The WalKR system controls major staphylococcal virulence genes and is involved in triggering the host inflammatory response. Infect Immun. 2012 Oct;80(10):3438-53. PMID:22825451 doi:10.1128/IAI.00195-12
- ↑ Kim T, Choi J, Lee S, Yeo KJ, Cheong HK, Kim KK. Structural Studies on the Extracellular Domain of Sensor Histidine Kinase YycG from Staphylococcus aureus and Its Functional Implications. J Mol Biol. 2016 Jul 4. pii: S0022-2836(16)30241-8. doi:, 10.1016/j.jmb.2016.06.019. PMID:27389096 doi:http://dx.doi.org/10.1016/j.jmb.2016.06.019
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