7ZKC

Catalytic domain of UDP-Glucose Glycoprotein Glucosyltransferase from Chaetomium thermophilum (apo form)

7ZKC の概要

• エントリーDOI: 10.2210/pdb7zkc/pdb
• 関連するPDBエントリー: 6FSN 7ZHB
• 分子名称: 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)
• 機能のキーワード: glycoprotein, misfolding, transferase, endoplasmic reticulum. udp-glucose, gt24
• 由来する生物種: Chaetomium thermophilum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35951.85

構造登録者

Roversi, P.,Zitzmann, N.,Bayo, Y.,Le Cornu, J.D. (登録日: 2022-04-12, 公開日: 2022-04-20, 最終更新日: 2024-11-13)

主引用文献

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

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: 37822503
DOI: 10.1016/j.isci.2023.107919

実験手法

X-RAY DIFFRACTION (1.769 Å)