2HWK

Crystal Structure of Venezuelan Equine Encephalitis Alphavirus nsP2 Protease Domain

2HWK の概要

• エントリーDOI: 10.2210/pdb2hwk/pdb
• 分子名称: helicase nsP2, FORMIC ACID (3 entities in total)
• 機能のキーワード: rossmann fold, alpha/beta/alpha, multi-domain, hydrolase
• 由来する生物種: Venezuelan equine encephalitis virus (strain TC-83)
• 細胞内の位置: Non-structural polyprotein: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . P123: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . P123': Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . mRNA-capping enzyme nsP1: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . Protease nsP2: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 3: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 3': Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . RNA-directed RNA polymerase nsP4: Host endosome membrane ; Peripheral membrane protein ; Cytoplasmic side : P27282
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36377.49

構造登録者

Russo, A.T.,White, M.A.,Watowich, S.J. (登録日: 2006-08-01, 公開日: 2006-09-26, 最終更新日: 2024-02-14)

主引用文献

Russo, A.T.,White, M.A.,Watowich, S.J.
The Crystal Structure of the Venezuelan Equine Encephalitis Alphavirus nsP2 Protease.
Structure, 14:1449-1458, 2006

PubMed Abstract: Alphavirus replication and propagation is dependent on the protease activity of the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into functional components. Thus, nsP2 is an attractive target for drug discovery efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral development has been hampered by a lack of structural information for the nsP2 protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro) from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution. The protease structure consists of two distinct domains. The nsP2pro N-terminal domain contains the catalytic dyad cysteine and histidine residues organized in a protein fold that differs significantly from any known cysteine protease or protein folds. The nsP2pro C-terminal domain displays structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases and provides essential elements that contribute to substrate recognition and may also regulate the structure of the substrate binding cleft.

PubMed: 16962975
DOI: 10.1016/j.str.2006.07.010

実験手法

X-RAY DIFFRACTION (2.45 Å)