This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
5ndf
From Proteopedia
(Difference between revisions)
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Small-molecule inhibition of ppGalNAc-Ts selectively reduces mucin-type O-glycosylation== | |
| + | <StructureSection load='5ndf' size='340' side='right'caption='[[5ndf]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ndf]] is a 6 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=5NDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NDF 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]] 2.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LU2:2-(3,4-DIHYDROXYPHENYL)-5,7-DIHYDROXY-4H-CHROMEN-4-ONE'>LU2</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=5ndf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ndf OCA], [https://pdbe.org/5ndf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ndf RCSB], [https://www.ebi.ac.uk/pdbsum/5ndf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ndf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GALT2_HUMAN GALT2_HUMAN] Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.<ref>PMID:9295285</ref> <ref>PMID:12438318</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mucin-type O-glycosylation is the most abundant type of O-glycosylation. It is initiated by the members of polypeptide N-acetyl-alpha-galactosaminyltransferase (ppGalNAc-T) family and closely associated with both physiological and pathological conditions such as coronary artery disease or Alzheimer' s disease. The lack of direct and selective inhibitors of ppGalNAc-Ts has largely impeded research progress in understanding the molecular events in mucin-type O-glycosylation. Here, we report that a small molecule, the plant flavonoid luteolin, selectively inhibits ppGalNAc-Ts in vitro and in cells. We found that luteolin inhibits ppGalNAc-T2 through a peptide/protein-competitive manner but not promiscuously, e.g. via aggregation-based activity. X-ray structural analysis revealed that luteolin binds to the PxP motif-binding site found in most protein substrates, which was further validated by comparing the interactions between luteolin with wildtype enzyme and mutants using 1H NMR-based binding experiments. Functional studies disclosed that luteolin at least partially reduced production of beta-amyloid (Abeta) protein by selectively inhibiting the activity of ppGalNAc-T isoforms. In conclusion, our study provides key structural and functional details on luteolin inhibiting ppGalNAc-T activity, opening up the way for further optimization of more potent and specific ppGalNAc-T inhibitors. Moreover, our findings may inform future investigations into site-specific O-GalNAc glycosylation and into the molecular mechanism of luteolin-mediated ppGalNAc-T inhibition. | ||
| - | + | The small molecule luteolin inhibits N-acetyl-alpha-galactosaminyltransferases and reduces mucin-type O-glycosylation of amyloid precursor protein.,Liu F, Xu K, Xu Z, Rivas ML, Li X, Lu J, Delso I, Merino P, Hurtado-Guerrero R, Zhang Y J Biol Chem. 2017 Oct 23. pii: jbc.M117.814202. doi: 10.1074/jbc.M117.814202. PMID:29061849<ref>PMID:29061849</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: De | + | <div class="pdbe-citations 5ndf" style="background-color:#fffaf0;"></div> |
| - | [[Category: Hurtado-Guerrero | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: De las Rivas M]] | ||
| + | [[Category: Hurtado-Guerrero R]] | ||
Current revision
Small-molecule inhibition of ppGalNAc-Ts selectively reduces mucin-type O-glycosylation
| |||||||||||
