8QF2

Beta-L-Arabinofurano-cyclitol Aziridines are Cysteine-directed Broad-spectrum Inhibitors and Activity-based Probes for Retaining Beta-L-arabinofuranosidases

これはPDB形式変換不可エントリーです。

8QF2 の概要

• エントリーDOI: 10.2210/pdb8qf2/pdb
• 分子名称: Non-reducing end beta-L-arabinofuranosidase, ZINC ION, (1~{S},2~{S},3~{S},4~{R})-4-azanyl-3-(hydroxymethyl)cyclopentane-1,2-diol, ... (4 entities in total)
• 機能のキーワード: arabinofuranosidase, activity-based probe, cyclophellitol aziridine, hydrolase
• 由来する生物種: Bifidobacterium longum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 74670.49

構造登録者

Borlandelli, V.,Offen, W.A.,Moroz, O.,Nin-Hill, A.,McGregor, N.,Binkhorst, L.,Armstrong, Z.,Ishiwata, A.,Artola, M.,Rovira, C.,Davies, G.J.,Overkleeft, H. (登録日: 2023-09-02, 公開日: 2023-12-13, 最終更新日: 2024-11-06)

主引用文献

Borlandelli, V.,Offen, W.,Moroz, O.,Nin-Hill, A.,McGregor, N.,Binkhorst, L.,Ishiwata, A.,Armstrong, Z.,Artola, M.,Rovira, C.,Davies, G.J.,Overkleeft, H.S.
beta-l- Arabino furano-cyclitol Aziridines Are Covalent Broad-Spectrum Inhibitors and Activity-Based Probes for Retaining beta-l-Arabinofuranosidases.
Acs Chem.Biol., 18:2564-2573, 2023

PubMed Abstract: GH127 and GH146 microorganismal retaining β-l-arabinofuranosidases, expressed by human gut microbiomes, feature an atypical catalytic domain and an unusual mechanism of action. We recently reported that both GH146 and HypBA1 are inhibited by β-l-furanosyl cyclophellitol epoxide, supporting the action of a zinc-coordinated cysteine as a catalytic nucleophile, where in most retaining GH families, an aspartate or glutamate is employed. This work presents a panel of β-l-furanosyl cyclophellitol epoxides and aziridines as mechanism-based GH146/HypBA1 inhibitors and activity-based probes. The β-l-furanosyl cyclophellitol aziridines both inhibit and label β-l-arabinofuranosidase efficiently (however with different activities), whereas the epoxide-derived probes favor GH146 over HypBA1. These findings are accompanied by X-ray structural analysis of the unmodified β-l-furanosyl cyclophellitol aziridine in complex with both isozymes, which were shown to react by nucleophilic opening of the aziridine, at the pseudoanomeric carbon, by the active site cysteine nucleophile to form a stable thioether bond. Altogether, our activity-based probes may serve as chemical tools for the detection and identification of low-abundance β-l-arabinofuranosidases in complex biological samples.

PubMed: 38051515
DOI: 10.1021/acschembio.3c00558

実験手法

X-RAY DIFFRACTION (2.35 Å)