5UQT

Clostridium difficile Toxin B (TcdB) glucosyltransferase domain co-crystallized with apigenin

5UQT の概要

• エントリーDOI: 10.2210/pdb5uqt/pdb
• 関連するPDBエントリー: 5UQK 5UQL 5UQM 5UQN
• 分子名称: Toxin B, MANGANESE (II) ION, 5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (3 entities in total)
• 機能のキーワード: glucosyltransferase, toxin, transferase
• 由来する生物種: Clostridioides difficile
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 131094.09

構造登録者

Alvin, J.W.,Lacy, D.B. (登録日: 2017-02-08, 公開日: 2017-05-10, 最終更新日: 2023-10-04)

主引用文献

Alvin, J.W.,Lacy, D.B.
Clostridium difficile toxin glucosyltransferase domains in complex with a non-hydrolyzable UDP-glucose analogue.
J. Struct. Biol., 198:203-209, 2017

PubMed Abstract: Clostridium difficile is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. The organism produces two homologous toxins, TcdA and TcdB, which enter and disrupt host cell function by glucosylating and thereby inactivating key signalling molecules within the host. As a toxin-mediated disease, there has been a significant interest in identifying small molecule inhibitors of the toxins' glucosyltransferase activities. This study was initiated as part of an effort to identify the mode of inhibition for a small molecule inhibitor of glucosyltransferase activity called apigenin. In the course of trying to get co-crystals with this inhibitor, we determined five different structures of the TcdA and TcdB glucosyltransferase domains and made use of a non-hydrolyzable UDP-glucose substrate. While we were able to visualize apigenin bound in one of our structures, the site was a crystal packing interface and not likely to explain the mode of inhibition. Nevertheless, the structure allowed us to capture an apo-state (one without the sugar nucleotide substrate) of the TcdB glycosyltransferase domain that had not been previously observed. Comparison of this structure with structures obtained in the presence of a non-hydrolyzable UDP-glucose analogue have allowed us to document multiple conformations of a C-terminal loop important for catalysis. We present our analysis of these five new structures with the hope that it will advance inhibitor design efforts for this important class of biological toxins.

PubMed: 28433497
DOI: 10.1016/j.jsb.2017.04.006

実験手法

X-RAY DIFFRACTION (2.75 Å)