View source for 9b70


==Cryo-EM structure of MraY in complex with analogue 2==
<StructureSection load='9b70' size='340' side='right'caption='[[9b70]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9b70]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9B70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B70 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]] 2.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AI1:(2S,3S)-2-{[(3-{[(2S)-6-amino-2-hexadecanamidohexanamido]methyl}phenyl)methyl]amino}-3-{[(2S,3R,4S,5R)-5-(aminomethyl)-3,4-dihydroxyoxolan-2-yl]oxy}-3-[(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]propanoic+acid+(non-preferred+name)'>A1AI1</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=9b70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b70 OCA], [https://pdbe.org/9b70 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b70 RCSB], [https://www.ebi.ac.uk/pdbsum/9b70 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b70 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MRAY_AQUAE MRAY_AQUAE] First step of the lipid cycle reactions in the biosynthesis of the cell wall peptidoglycan (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.

Development of a natural product optimization strategy for inhibitors against MraY, a promising antibacterial target.,Yamamoto K, Sato T, Hao A, Asao K, Kaguchi R, Kusaka S, Ruddarraju RR, Kazamori D, Seo K, Takahashi S, Horiuchi M, Yokota SI, Lee SY, Ichikawa S Nat Commun. 2024 Jun 14;15(1):5085. doi: 10.1038/s41467-024-49484-7. PMID:38877016<ref>PMID:38877016</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9b70" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus VF5]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Hao A]]
[[Category: Lee S-Y]]