View source for 6jbh


==Cryo-EM structure and transport mechanism of a wall teichoic acid ABC transporter==
<SX load='6jbh' size='340' side='right' viewer='molstar' caption='[[6jbh]], [[Resolution|resolution]] 3.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jbh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Alicyclobacillus_herbarius Alicyclobacillus herbarius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JBH 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]] 3.94&#8491;</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=6jbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jbh OCA], [https://pdbe.org/6jbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jbh RCSB], [https://www.ebi.ac.uk/pdbsum/6jbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jbh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A6I8WFL6_9BACL A0A6I8WFL6_9BACL] 
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== Publication Abstract from PubMed ==
The wall teichoic acid (WTA) is a major cell wall component of Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common cause of fatal clinical infections in humans. Thus, the indispensable ABC transporter TarGH, which flips WTA from cytoplasm to extracellular space, becomes a promising target of anti-MRSA drugs. Here, we report the 3.9-A cryo-electron microscopy (cryo-EM) structure of a 50% sequence-identical homolog of TarGH from Alicyclobacillus herbarius at an ATP-free and inward-facing conformation. Structural analysis combined with activity assays enables us to clearly decode the binding site and inhibitory mechanism of the anti-MRSA inhibitor Targocil, which targets TarGH. Moreover, we propose a "crankshaft conrod" mechanism utilized by TarGH, which can be applied to similar ABC transporters that translocate a rather big substrate through relatively subtle conformational changes. These findings provide a structural basis for the rational design and optimization of antibiotics against MRSA.IMPORTANCE The wall teichoic acid (WTA) is a major component of cell wall and a pathogenic factor in methicillin-resistant Staphylococcus aureus (MRSA). The ABC transporter TarGH is indispensable for flipping WTA precursor from cytoplasm to the extracellular space, thus making it a promising drug target for anti-MRSA agents. The 3.9-A cryo-EM structure of a TarGH homolog helps us to decode the binding site and inhibitory mechanism of a recently reported inhibitor, Targocil, and provides a structural platform for rational design and optimization of potential antibiotics. Moreover, we propose a "crankshaft conrod" mechanism to explain how a big substrate is translocated through subtle conformational changes of type II exporters. These findings advance our understanding of anti-MRSA drug design and ABC transporters.

Cryo-electron Microscopy Structure and Transport Mechanism of a Wall Teichoic Acid ABC Transporter.,Chen L, Hou WT, Fan T, Liu B, Pan T, Li YH, Jiang YL, Wen W, Chen ZP, Sun L, Zhou CZ, Chen Y mBio. 2020 Mar 17;11(2). pii: mBio.02749-19. doi: 10.1128/mBio.02749-19. PMID:32184247<ref>PMID:32184247</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6jbh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
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[[Category: Alicyclobacillus herbarius]]
[[Category: Large Structures]]
[[Category: Chen L]]
[[Category: Chen Y]]
[[Category: Fan T]]
[[Category: Hou WT]]
[[Category: Jiang YL]]
[[Category: Li YH]]
[[Category: Liu BH]]
[[Category: Sun LF]]
[[Category: Zhou CZ]]