3ZFU

Crystal structure of substrate-like, unprocessed N-terminal protease Npro mutant S169P with sulphate

3ZFU の概要

• エントリーDOI: 10.2210/pdb3zfu/pdb
• 関連するPDBエントリー: 3ZFN 3ZFO 3ZFP 3ZFQ 3ZFR 3ZFT
• 分子名称: N-TERMINAL PROTEASE NPRO, MONOTHIOGLYCEROL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, auto-processing cysteine protease, viral protease, in cis- cleavage, hydroxide-dependent catalysis, auto-proteolysis, immune modulation, host-pathogen interaction, convergent evolution
• 由来する生物種: PESTIVIRUS STRAIN D32/00_HOBI
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18600.32

構造登録者

Zogg, T.,Sponring, M.,Schindler, S.,Koll, M.,Schneider, R.,Brandstetter, H.,Auer, B. (登録日: 2012-12-12, 公開日: 2013-05-15, 最終更新日: 2024-10-23)

主引用文献

Zogg, T.,Sponring, M.,Schindler, S.,Koll, M.,Schneider, R.,Brandstetter, H.,Auer, B.
Crystal Structures of the Viral Protease Npro Imply Distinct Roles for the Catalytic Water in Catalysis
Structure, 21:929-, 2013

PubMed Abstract: Npro is a key effector protein of pestiviruses such as bovine viral diarrhea virus and abolishes host cell antiviral defense mechanisms. Synthesized as the N-terminal part of the viral polyprotein, Npro releases itself via an autoproteolytic cleavage, triggering its immunological functions. However, the mechanisms of its proteolytic action and its immune escape were unclear. Here, we present the crystal structures of Npro to 1.25 Å resolution. Structures of pre- and postcleavage intermediates identify three catalytically relevant elements. The trapping of the putative catalytic water reveals its distinct roles as a base, acid, and nucleophile. The presentation of the substrate further explains the enigmatic latency of the protease, ensuring a single in cis cleavage. Additionally, we identified a zinc-free, disulfide-linked conformation of the TRASH motif, an interaction hub of immune factors. The structure opens additional opportunities in utilizing Npro as an autocleaving fusion protein and as a pharmaceutical target.

PubMed: 23643950
DOI: 10.1016/J.STR.2013.04.003

実験手法

X-RAY DIFFRACTION (1.76 Å)