8P61

Crystal structure of O'nyong'nyong virus capsid protease (106-256)

8P61 の概要

• エントリーDOI: 10.2210/pdb8p61/pdb
• 分子名称: Capsid protein, GLYCEROL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: capsid protease, onyongnyong virus, alphaviruses, virus
• 由来する生物種: O'nyong-nyong virus strain Gulu
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67992.77

構造登録者

Plewka, J.,Chykunova, Y.,Wilk, P.,Sienczyk, M.,Dubin, G.,Pyrc, K. (登録日: 2023-05-24, 公開日: 2024-03-06, 最終更新日: 2024-05-15)

主引用文献

Chykunova, Y.,Plewka, J.,Wilk, P.,Sienczyk, M.,Dubin, G.,Pyrc, K.
Autoinhibition of suicidal capsid protease from O'nyong'nyong virus.
Int.J.Biol.Macromol., 262:130136-130136, 2024

PubMed Abstract: Alphaviruses pose a significant threat to public health. Capsid protein encoded in the alphaviral genomes constitutes an interesting therapy target, as it also serves as a protease (CP). Remarkably, it undergoes autoproteolysis, leading to the generation of the C-terminal tryptophan that localizes to the active pocket, deactivating the enzyme. Lack of activity hampers the viral replication cycle, as the virus is not capable of producing the infectious progeny. We investigated the structure and function of the CP encoded in the genome of O'nyong'nyong virus (ONNV), which has instigated outbreaks in Africa. Our research provides a high-resolution crystal structure of the ONNV CP in its active state and evaluates the enzyme's activity. Furthermore, we demonstrated a dose-dependent reduction in ONNV CP proteolytic activity when exposed to indole, suggesting that tryptophan analogs may be a promising basis for developing small molecule inhibitors. It's noteworthy that the capsid protease plays an essential role in virus assembly, binding viral glycoproteins through its glycoprotein-binding hydrophobic pocket. We showed that non-aromatic cyclic compounds like dioxane disrupt this vital interaction. Our findings provide deeper insights into ONNV's biology, and we believe they will prove instrumental in guiding the development of antiviral strategies against arthritogenic alphaviruses.

PubMed: 38354926
DOI: 10.1016/j.ijbiomac.2024.130136

実験手法

X-RAY DIFFRACTION (1.9 Å)