6paj

From Proteopedia

(Difference between revisions)

Revision as of 15:25, 8 June 2021

Structure of the SrrAB Histidine Kinase DHp-CA domain

Structural highlights

6paj is a 2 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	srrB ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885)
Activity:	Histidine kinase, with EC number 2.7.13.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]

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^[1]

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

References

↑ 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. The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines. Proc Natl Acad Sci U S A. 2020 Apr 30. pii: 1921307117. doi:, 10.1073/pnas.1921307117. PMID:32354997 doi:http://dx.doi.org/10.1073/pnas.1921307117

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/6paj"

@@ Line 3: / Line 3: @@
 <StructureSection load='6paj' size='340' side='right'caption='[[6paj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6paj]] is a 2 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=6PAJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PAJ FirstGlance]. <br>
+<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 ([http://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='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'>[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='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>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6paj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6paj OCA], [http://pdbe.org/6paj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6paj RCSB], [http://www.ebi.ac.uk/pdbsum/6paj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6paj 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=6paj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6paj OCA], [https://pdbe.org/6paj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6paj RCSB], [https://www.ebi.ac.uk/pdbsum/6paj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6paj ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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]
+[[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]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

6paj

From Proteopedia

Revision as of 15:25, 8 June 2021

Structure of the SrrAB Histidine Kinase DHp-CA domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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