7OMS

Bs164 in complex with mannocyclophellitol aziridine

これはPDB形式変換不可エントリーです。

7OMS の概要

• エントリーDOI: 10.2210/pdb7oms/pdb
• 分子名称: Glyco_hydro_42M domain-containing protein, 1,2-ETHANEDIOL, (1~{R},2~{R},3~{S},4~{R},5~{R},6~{R})-5-(hydroxymethyl)-7-azabicyclo[4.1.0]heptane-2,3,4-triol, ... (5 entities in total)
• 機能のキーワード: inhibitor complex, hydrolase
• 由来する生物種: Bacteroides salyersiae
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 462210.94

構造登録者

McGregor, N.,Beenakker, T.,Kuo, C.L.,Wong, C.S.,Offren, W.A.,Armstrong, Z.,Codee, J.D.C.,Aerts, J.M.F.G.,Florea, B.I.,Overkleeft, H.,Davies, G.J. (登録日: 2021-05-24, 公開日: 2022-02-02, 最終更新日: 2024-11-13)

主引用文献

McGregor, N.G.S.,Kuo, C.L.,Beenakker, T.J.M.,Wong, C.S.,Offen, W.A.,Armstrong, Z.,Florea, B.I.,Codee, J.D.C.,Overkleeft, H.S.,Aerts, J.M.F.G.,Davies, G.J.
Synthesis of broad-specificity activity-based probes for exo -beta-mannosidases.
Org.Biomol.Chem., 20:877-886, 2022

PubMed Abstract: -β-mannosidases are a broad class of stereochemically retaining hydrolases that are essential for the breakdown of complex carbohydrate substrates found in all kingdoms of life. Yet the detection of -β-mannosidases in complex biological samples remains challenging, necessitating the development of new methodologies. Cyclophellitol and its analogues selectively label the catalytic nucleophiles of retaining glycoside hydrolases, making them valuable tool compounds. Furthermore, cyclophellitol can be readily redesigned to enable the incorporation of a detection tag, generating activity-based probes (ABPs) that can be used to detect and identify specific glycosidases in complex biological samples. Towards the development of ABPs for -β-mannosidases, we present a concise synthesis of β--configured cyclophellitol, cyclophellitol aziridine, and -alkyl cyclophellitol aziridines. We show that these probes covalently label -β-mannosidases from GH families 2, 5, and 164. Structural studies of the resulting complexes support a canonical mechanism-based mode of action in which the active site nucleophile attacks the pseudoanomeric centre to form a stable ester linkage, mimicking the glycosyl enzyme intermediate. Furthermore, we demonstrate activity-based protein profiling using an -alkyl aziridine derivative by specifically labelling MANBA in mouse kidney tissue. Together, these results show that synthetic -configured cyclophellitol analogues hold promise for detecting -β-mannosidases in biological and biomedical research.

PubMed: 35015006
DOI: 10.1039/d1ob02287c

実験手法

X-RAY DIFFRACTION (2.05 Å)