7ARA

Rhinovirus A2 2A protease in complex with zVAM.fmk

7ARA の概要

• エントリーDOI: 10.2210/pdb7ara/pdb
• 分子名称: 2A protease, (phenylmethyl) ~{N}-[(2~{R})-3-methyl-1-[[(2~{S})-1-[[(3~{S})-1-methylsulfanyl-4-oxidanylidene-pentan-3-yl]amino]-1-oxidanylidene-propan-2-yl]amino]-1-oxidanylidene-butan-2-yl]carbamate, ZINC ION, ... (5 entities in total)
• 機能のキーワード: chymotrypsin-like cysteine protease, rhinoviral 2a protease, zvam.fmk, viral protein
• 由来する生物種: Human rhinovirus 2 (HRV-2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33486.31

構造登録者

Deutschmann-Olek, K.M.,Skern, T.,Bezerra, G.A.,Yue, W.W. (登録日: 2020-10-23, 公開日: 2021-07-28, 最終更新日: 2024-10-09)

主引用文献

Deutschmann-Olek, K.M.,Yue, W.W.,Bezerra, G.A.,Skern, T.
Defining substrate selection by rhinoviral 2A proteinase through its crystal structure with the inhibitor zVAM.fmk.
Virology, 562:128-141, 2021

PubMed Abstract: Picornavirus family members cause disease in humans. Human rhinoviruses (RV), the main causative agents of the common cold, increase the severity of asthma and COPD; hence, effective agents against RVs are required. The 2A proteinase (2A), found in all enteroviruses, represents an attractive target; inactivating mutations in poliovirus 2A result in an extension of the VP1 protein preventing infectious virion assembly. Variations in sequence and substrate specificity on eIF4G isoforms between RV 2A of genetic groups A and B hinder 2A as drug targets. Here, we demonstrate that although RV-A2 and RV-B4 2A cleave the substrate GAB1 at different sites, the 2A from both groups cleave equally efficiently an artificial site containing P1 methionine. We determined the RV-A2 2A structure complexed with zVAM.fmk, containing P1 methionine. Analysis of this first 2A-inhibitor complex reveals a conserved hydrophobic P4 pocket among enteroviral 2A as a potential target for broad-spectrum anti-enteroviral inhibitors.

PubMed: 34315103
DOI: 10.1016/j.virol.2021.07.008

実験手法

X-RAY DIFFRACTION (2.243 Å)