24 糖タンパク質折り畳みセンサー酵素UGGTの基質特異性解析(口頭発表の部)

概要

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The folding of glycoproteins is mediated by a quality control system (Figure 1) in the endoplasmic reticulum, where UDP-Glc: glycoprotein glucosyltransferase (UGGT) serves as a "folding sensor". In this study, we focused on the molecular basis for substrate-recognition by UGGT. To obtain precise understanding of the recognition mode of this folding sensor enzyme, we synthesized various systematic inhibitors (Figure 3) and high-mannose-type glycans modified with various types of aglycon (Figure 4 and Figure 5). Comparison of their inhibitory activity (Figure 3) or reactivity (Figure 5) provided support for the hypothesis that UGGT recognizes the innermost GlcNAc residue and the hydrophobic region of client glycoproteins. Through these experiments, we found efficient acceptor substrates for UGGT. In particular, introduction of Fmoc into the aglycon, made glycans highly reactive to UGGT (compound 8 in Figure 4). Derivatives carrying fluorescent functional group TAMRA or BODIPY are also excellent substrates (compound 9 and 10 in Figure 4) and expected to be valuable for detecting the activity of UGGT.
天然有機化合物討論会の論文
2008-09-01