View source for 9cfl


==Cryo-EM structure of S. aureus TarGH in complex with ATP-gamma-S==
<StructureSection load='9cfl' size='340' side='right'caption='[[9cfl]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9cfl]] is a 4 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=9CFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CFL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=AV0:(2~{R},3~{R},4~{S},5~{S},6~{R})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-6-[2-decyl-2-[[(2~{R},3~{R},4~{R},5~{S},6~{R})-6-(hydroxymethyl)-5-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-3,4-bis(oxidanyl)oxan-2-yl]oxymethyl]dodecoxy]-2-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol'>AV0</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9cfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9cfl OCA], [https://pdbe.org/9cfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9cfl RCSB], [https://www.ebi.ac.uk/pdbsum/9cfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9cfl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H2XIF1_STAA3 A0A0H2XIF1_STAA3] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Wall teichoic acid (WTA) is a polyol phosphate polymer that covalently decorates peptidoglycan of gram-positive bacteria, including Staphylococcus aureus. Central to WTA biosynthesis is flipping of lipid-linked precursors across the cell membrane by TarGH, a type V ABC transporter. Here, we present cryo-EM structures of S. aureus TarGH in the presence of targocil-II, a promising small-molecule lead with beta-lactam antibiotic synergistic action. Targocil-II binds to the extracellular dimerisation interface of TarG, we suggest mimicking flipped but not yet released substrate. In absence of targocil-II and in complex with ATP analogue ATPgammaS, determined at 2.3 A resolution, the ATPase active site is allosterically inhibited. This is due to a so far undescribed D-loop conformation, potentially minimizing spurious ATP hydrolysis in the absence of substrate. Targocil-II binding comparatively causes local and remote conformational changes through to the TarH active site, with the D-loop now optimal for ATP hydrolysis. These structures suggest an ability to modulate ATP hydrolysis in a WTA substrate dependent manner and a jammed ATPase cycle as the basis of the observed inhibition by targocil-II. The molecular insights provide an unprecedented basis for development of TarGH targeted therapeutics for treatment of multidrug-resistant S. aureus and other gram-positive bacterial infections.

Cryo-EM analyses unveil details of mechanism and targocil-II mediated inhibition of S. aureus WTA transporter TarGH.,Li FKK, Peters SC, Worrall LJ, Sun T, Hu J, Vuckovic M, Farha M, Palacios A, Caveney NA, Brown ED, Strynadka NCJ Nat Commun. 2025 Apr 4;16(1):3224. doi: 10.1038/s41467-025-58202-w. PMID:40185711<ref>PMID:40185711</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9cfl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Li FKK]]
[[Category: Strynadka NCJ]]
[[Category: Worrall LJ]]