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'''Unreleased structure'''


The entry 9znn is ON HOLD
==Cryo-EM structure of human UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) in complex with APPB==
<StructureSection load='9znn' size='340' side='right'caption='[[9znn]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9znn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ZNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZNN 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C3G:4-({(2S,3S)-1-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]-1-oxopropan-2-yl}amino)-N-[(4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl)methyl]butanamide+(non-preferred+name)'>A1C3G</scene>, <scene name='pdbligand=A1C3H:[(2~{R})-3-[[(2~{R})-2,3-bis(oxidanyl)propoxy]-oxidanyl-phosphoryl]oxy-2-[(~{Z})-octadec-9-enoyl]oxy-propyl]+(~{Z})-octadec-9-enoate'>A1C3H</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=9znn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9znn OCA], [https://pdbe.org/9znn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9znn RCSB], [https://www.ebi.ac.uk/pdbsum/9znn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9znn ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glycoconjugates facilitate myriad biological processes, including cell-cell recognition and immune response, and they are generated by enzymes that transfer glycans. The orthologs MraY and DPAGT1 are dimeric phosphoglycosyltransferases involved in oligosaccharide biosynthesis for either bacterial peptidoglycan or eukaryotic N-linked glycans, respectively. Both enzymes play central regulatory roles, making them attractive targets for antibacterial and anticancer therapies. In our prior studies, a muraymycin A1-derived inhibitor termed APPB (aminouridyl phenoxypiperidinbenzyl butanamide) was developed. It exhibits sub-100 nM IC50 values against both MraY and DPAGT1 and has demonstrated efficacy against DPAGT1-dependent cancers, making it an excellent starting point for next-generation small molecules. To guide inhibitor development, we determined cryo-EM structures of APPB bound to MraY or DPAGT1 at 2.9 A resolution using single-particle analysis. The structures reveal that APPB, composed of a nucleoside, a central amide, and a lipid-mimetic, adopts two conformations in each protein, which correlate with local hydrogen-bonding contacts of the central amide carbonyl. Examination of the amide carbonyl environments guides conformer selection for future DPAGT1-targeting anticancer agents. Further, comparisons of APPB-bound geometries and nucleoside interactions inform opportunities for antibacterial agents targeting MraY. Overall, our study provides design principles for MraY- or DPAGT1-specific drugs and motivates the utility of simultaneously characterizing inhibitor-bound orthologs for selective therapeutics.


Authors: Kirsh, J.M., Ochoa, J.M., Soroush-Pejrimovsky, M.T., Kaudeer, B.Y., Clemons, W.M.
Structures of bacterial and human phosphoglycosyltransferases bound to a common inhibitor inform selective therapeutics.,Kaudeer BY, Kirsh JM, Mitachi K, Ochoa JM, Soroush-Pejrimovsky MT, Li YE, Nguyen VN, Kurosu M, Clemons WM Jr bioRxiv [Preprint]. 2025 Dec 16:2025.12.16.694696. doi: , 10.64898/2025.12.16.694696. PMID:41446129<ref>PMID:41446129</ref>


Description: Cryo-EM structure of human UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) in complex with APPB
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Soroush-Pejrimovsky, M.T]]
<div class="pdbe-citations 9znn" style="background-color:#fffaf0;"></div>
[[Category: Kaudeer, B.Y]]
== References ==
[[Category: Kirsh, J.M]]
<references/>
[[Category: Ochoa, J.M]]
__TOC__
[[Category: Clemons, W.M]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Clemons WM]]
[[Category: Kaudeer BY]]
[[Category: Kirsh JM]]
[[Category: Ochoa JM]]
[[Category: Soroush-Pejrimovsky MT]]
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