5E6J

Structure of SARS PLpro bound to a Lys48-linked di-ubiquitin activity based probe

5E6J の概要

• エントリーDOI: 10.2210/pdb5e6j/pdb
• 分子名称: Replicase polyprotein 1ab, ubiquitin, Polyubiquitin-B, ... (6 entities in total)
• 機能のキーワード: sars plpro, deubiquitinating enzyme, ubiquitin, activity based probe, k48-linkage, hydrolase
• 由来する生物種: Human SARS coronavirus (SARS-CoV); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 107784.14

構造登録者

Lima, C.D.,Bekes, M. (登録日: 2015-10-09, 公開日: 2016-05-18, 最終更新日: 2023-11-15)

主引用文献

Bekes, M.,van der Heden van Noort, G.J.,Ekkebus, R.,Ovaa, H.,Huang, T.T.,Lima, C.D.
Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.
Mol. Cell, 62:572-585, 2016

PubMed Abstract: Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.

PubMed: 27203180
DOI: 10.1016/j.molcel.2016.04.016

実験手法

X-RAY DIFFRACTION (2.85 Å)