View source for 8tjc


==Structure of human beta 1,3-N-acetylglucosaminyltransferase 2 with compound 8a==
<StructureSection load='8tjc' size='340' side='right'caption='[[8tjc]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tjc]] is a 4 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=8TJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TJC 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=HI8:3-[(2~{R})-3,3-dimethylbutan-2-yl]-5-[(5~{S})-5-methyl-4-oxidanylidene-5-phenyl-1~{H}-imidazol-2-yl]-1~{H}-benzimidazol-2-one'>HI8</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=8tjc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tjc OCA], [https://pdbe.org/8tjc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tjc RCSB], [https://www.ebi.ac.uk/pdbsum/8tjc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tjc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B3GN2_HUMAN B3GN2_HUMAN] Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains. Shows a marked preference for Gal(beta1-4)Glc(NAc)-based acceptors (PubMed:9892646). Probably constitutes the main polylactosamine synthase.<ref>PMID:11042166</ref> <ref>PMID:25279697</ref> <ref>PMID:9892646</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
B3GNT2 is responsible for elongation of cell surface long-chain polylactosamine, which influences the regulation of the immune response, making it an attractive target for immunomodulation. In the development of amide containing B3GNT2 inhibitors guided by structure-based drug design, imidazolones were found to successfully serve as amide bioisosteres. This novel imidazolone isosteric strategy alleviated torsional strain of the amide bond on binding to B3GNT2 and improved potency, isoform selectivity, as well as certain physicochemical and pharmacokinetic properties. Herein, we present the synthesis, SAR, X-ray cocrystal structures, and in vivo PK properties of imidazol-4-ones in the context of B3GNT2 inhibition.

Imidazolone as an Amide Bioisostere in the Development of beta-1,3-N-Acetylglucosaminyltransferase 2 (B3GNT2) Inhibitors.,Jackson JJ, Siegmund AC, Bai WJ, Reed AB, Birkholz AB, Campuzano IDG, Crequer-Grandhomme A, Hu R, Modak RV, Sudom A, Javier N, Sanders C, Lo MC, Xie F, Cee VJ, Manzanillo P, Allen JG J Med Chem. 2023 Dec 14;66(23):16120-16140. doi: 10.1021/acs.jmedchem.3c01517. , Epub 2023 Nov 21. PMID:37988652<ref>PMID:37988652</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8tjc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Min X]]
[[Category: Sudom A]]