5F84

Crystal structure of Drosophila Poglut1 (Rumi) complexed with its glycoprotein product (glucosylated EGF repeat) and UDP

5F84 の概要

• エントリーDOI: 10.2210/pdb5f84/pdb
• 関連するPDBエントリー: 5F85 5F86 5F87
• 分子名称: O-glucosyltransferase rumi, Coagulation factor IX, URIDINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: glycosyltransferase, protein o-glucosyltransferase, notch regulation, egf repeat, transferase-hydrolase complex, transferase/hydrolase
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53595.03

構造登録者

Yu, H.J.,Li, H.L. (登録日: 2015-12-09, 公開日: 2016-07-20, 最終更新日: 2024-10-23)

主引用文献

Yu, H.,Takeuchi, H.,Takeuchi, M.,Liu, Q.,Kantharia, J.,Haltiwanger, R.S.,Li, H.
Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations.
Nat. Chem. Biol., 12:735-740, 2016

PubMed Abstract: Rumi O-glucosylates the EGF repeats of a growing list of proteins essential in metazoan development, including Notch. Rumi is essential for Notch signaling, and Rumi dysregulation is linked to several human diseases. Despite Rumi's critical roles, it is unknown how Rumi glucosylates a serine of many but not all EGF repeats. Here we report crystal structures of Drosophila Rumi as binary and ternary complexes with a folded EGF repeat and/or donor substrates. These structures provide insights into the catalytic mechanism and show that Rumi recognizes structural signatures of the EGF motif, the U-shaped consensus sequence, C-X-S-X-(P/A)-C and a conserved hydrophobic region. We found that five Rumi mutations identified in cancers and Dowling-Degos disease are clustered around the enzyme active site and adversely affect its activity. Our study suggests that loss of Rumi activity may underlie these diseases, and the mechanistic insights may facilitate the development of modulators of Notch signaling.

PubMed: 27428513
DOI: 10.1038/nchembio.2135

実験手法

X-RAY DIFFRACTION (2.5 Å)