7ZKC
Catalytic domain of UDP-Glucose Glycoprotein Glucosyltransferase from Chaetomium thermophilum (apo form)
Summary for 7ZKC
| Entry DOI | 10.2210/pdb7zkc/pdb |
| Related | 6FSN 7ZHB |
| Descriptor | UDP-glucose-glycoprotein glucosyltransferase-like protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | glycoprotein, misfolding, transferase, endoplasmic reticulum. udp-glucose, gt24 |
| Biological source | Chaetomium thermophilum |
| Total number of polymer chains | 1 |
| Total formula weight | 35951.85 |
| Authors | Roversi, P.,Zitzmann, N.,Bayo, Y.,Le Cornu, J.D. (deposition date: 2022-04-12, release date: 2022-04-20, Last modification date: 2024-11-13) |
| Primary citation | Guay, K.P.,Ibba, R.,Kiappes, J.L.,Vasiljevic, S.,Boni, F.,De Benedictis, M.,Zeni, I.,Le Cornu, J.D.,Hensen, M.,Chandran, A.V.,Kantsadi, A.L.,Caputo, A.T.,Blanco Capurro, J.I.,Bayo, Y.,Hill, J.C.,Hudson, K.,Lia, A.,Brun, J.,Withers, S.G.,Marti, M.,Biasini, E.,Santino, A.,De Rosa, M.,Milani, M.,Modenutti, C.P.,Hebert, D.N.,Zitzmann, N.,Roversi, P. A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint. Iscience, 26:107919-107919, 2023 Cited by PubMed Abstract: Misfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a UGGT "WY" conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases. 5M-8OH-Q has a 47 μM binding affinity for UGGT as measured by ligand-enhanced fluorescence. , 5M-8OH-Q inhibits both human UGGT isoforms at concentrations higher than 750 μM. 5M-8OH-Q binding to UGGT appears to be mutually exclusive to M5-9 glycan binding in an competition experiment. A medicinal program based on 5M-8OH-Q will yield the next generation of UGGT inhibitors. PubMed: 37822503DOI: 10.1016/j.isci.2023.107919 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.769 Å) |
Structure validation
Download full validation report
