6paj

<table><tr><td colspan='2'>[[6paj]] is a 2 chain structure with sequence from [https://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=6PAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PAJ FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">srrB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histidine_kinase Histidine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.13.3 2.7.13.3] </span></td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/SRRB_STAAU SRRB_STAAU]] Member of the two-component regulatory system SrrA/SrrB, which is involved in the global regulation of staphylococcal virulence factors in response to environmental oxygen levels as well as biofilm formation. Plays also an essential role in host-derived nitric oxide resistance by regulating hmp/flavohemoglobin, an enzyme that detoxifies nitric oxide by converting it to nitrate. Functions as a sensor protein kinase which is autophosphorylated at a histidine residue and transfers its phosphate group to SrrA. In turn, SrrA binds to the upstream promoter regions of the target genes to positively and negatively regulate their expression.[UniProtKB:Q5HFT1]

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== Publication Abstract from PubMed ==

Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.

The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines.,Tiwari N, Lopez-Redondo M, Miguel-Romero L, Kulhankova K, Cahill MP, Tran PM, Kinney KJ, Kilgore SH, Al-Tameemi H, Herfst CA, Tuffs SW, Kirby JR, Boyd JM, McCormick JK, Salgado-Pabon W, Marina A, Schlievert PM, Fuentes EJ Proc Natl Acad Sci U S A. 2020 Apr 30. pii: 1921307117. doi:, 10.1073/pnas.1921307117. PMID:32354997<ref>PMID:32354997</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Histidine kinase]]

[[Category: Moreno, A Marina]]

[[Category: Redondo, M L.Lopez]]

[[Category: Dimer]]

[[Category: Sensor protein]]