View source for 7mcy


==Crystal structure of Staphylococcus aureus Cystathionine gamma lyase, Holoenzyme with bound NL3==
<StructureSection load='7mcy' size='340' side='right'caption='[[7mcy]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mcy]] 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=7MCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MCY 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]] 1.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NL3:3-{[6-(7-chloro-1-benzothiophen-2-yl)-1H-indol-1-yl]methyl}-1H-pyrazole-5-carboxylic+acid'>NL3</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=7mcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mcy OCA], [https://pdbe.org/7mcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mcy RCSB], [https://www.ebi.ac.uk/pdbsum/7mcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mcy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H3K724_STAAE A0A0H3K724_STAAE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine gamma-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial H2S as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.

Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.,Shatalin K, Nuthanakanti A, Kaushik A, Shishov D, Peselis A, Shamovsky I, Pani B, Lechpammer M, Vasilyev N, Shatalina E, Rebatchouk D, Mironov A, Fedichev P, Serganov A, Nudler E Science. 2021 Jun 11;372(6547):1169-1175. doi: 10.1126/science.abd8377. PMID:34112687<ref>PMID:34112687</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mcy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cystathionine beta-lyase|Cystathionine beta-lyase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Kaushik A]]
[[Category: Nuthanakanti A]]
[[Category: Serganov A]]