View source for 7mq3


==C9A N55A Streptococcus pneumoniae CstR in the reduced state==
<StructureSection load='7mq3' size='340' side='right'caption='[[7mq3]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mq3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_D39 Streptococcus pneumoniae D39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MQ3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7mq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mq3 OCA], [https://pdbe.org/7mq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mq3 RCSB], [https://www.ebi.ac.uk/pdbsum/7mq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mq3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H2ZNA4_STRP2 A0A0H2ZNA4_STRP2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CstR is a persulfide-sensing member of the functionally diverse copper-sensitive operon repressor (CsoR) superfamily. While CstR regulates the bacterial response to hydrogen sulfide (H2S) and more oxidized reactive sulfur species (RSS) in Gram-positive pathogens, other dithiol-containing CsoR proteins respond to host derived Cu(I) toxicity, sometimes in the same bacterial cytoplasm, but without regulatory crosstalk in cells. It is not clear what prevents this crosstalk, nor the extent to which RSS sensors exhibit specificity over other oxidants. Here, we report a sequence similarity network (SSN) analysis of the entire CsoR superfamily, which together with the first crystallographic structure of a CstR and comprehensive mass spectrometry-based kinetic profiling experiments, reveal new insights into the molecular basis of RSS specificity in CstRs. We find that the more N-terminal cysteine is the attacking Cys in CstR and is far more nucleophilic than in a CsoR. Moreover, our CstR crystal structure is markedly asymmetric and chemical reactivity experiments reveal the functional impact of this asymmetry. Substitution of the Asn wedge between the resolving and the attacking thiol with Ala significantly decreases asymmetry in the crystal structure and markedly impacts the distribution of species, despite adopting the same global structure as the parent repressor. Companion NMR, SAXS and molecular dynamics simulations reveal that the structural and functional asymmetry can be traced to fast internal dynamics of the tetramer. Furthermore, this asymmetry is preserved in all CstRs and with all oxidants tested, giving rise to markedly distinct distributions of crosslinked products. Our exploration of the sequence, structural, and kinetic features that determine oxidant-specificity suggest that the product distribution upon RSS exposure is determined by internal flexibility.

Functional asymmetry and chemical reactivity of CsoR family persulfide sensors.,Fakhoury JN, Zhang Y, Edmonds KA, Bringas M, Luebke JL, Gonzalez-Gutierrez G, Capdevila DA, Giedroc DP Nucleic Acids Res. 2021 Dec 2;49(21):12556-12576. doi: 10.1093/nar/gkab1040. PMID:34755876<ref>PMID:34755876</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mq3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae D39]]
[[Category: Fakhoury J]]
[[Category: Giedroc DP]]
[[Category: Gonzalez-Gutierrez G]]