View source for 8cxr


==Crystal structure of MraY bound to a sphaerimicin analogue==
<StructureSection load='8cxr' size='340' side='right'caption='[[8cxr]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8cxr]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] 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=8CXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CXR 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]] 3.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P5L:(1S,4R,5S,6R,7S,9S,10S,11S,13S,14R)-9-[(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]-14-(hexadecanoyloxy)-5,6,13-trihydroxy-8,16-dioxa-2,11-diazatricyclo[9.3.1.1~4,7~]hexadecane-10-carboxylic+acid'>P5L</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=8cxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cxr OCA], [https://pdbe.org/8cxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cxr RCSB], [https://www.ebi.ac.uk/pdbsum/8cxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cxr ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria.

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.,Nakaya T, Yabe M, Mashalidis EH, Sato T, Yamamoto K, Hikiji Y, Katsuyama A, Shinohara M, Minato Y, Takahashi S, Horiuchi M, Yokota SI, Lee SY, Ichikawa S Nat Commun. 2022 Dec 20;13(1):7575. doi: 10.1038/s41467-022-35227-z. PMID:36539416<ref>PMID:36539416</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8cxr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Lee SY]]
[[Category: Mashalidis EH]]