8GYA

Crystal structure of Alongshan virus methyltransferase bound to Sinefungin

8GYA の概要

• エントリーDOI: 10.2210/pdb8gya/pdb
• 分子名称: Methyltransferase, SINEFUNGIN (3 entities in total)
• 機能のキーワード: methyltransferase, viral protein
• 由来する生物種: Alongshan virus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64473.71

構造登録者

Chen, H.,Lin, S.,Lu, G.W. (登録日: 2022-09-21, 公開日: 2023-09-27, 最終更新日: 2026-03-11)

主引用文献

Chen, H.,Lin, S.,Yang, F.,Chen, Z.,Guo, L.,Yang, J.,Lin, X.,Wang, L.,Duan, Y.,Wen, A.,Zhang, X.,Dai, Y.,Yin, K.,Yuan, X.,Yu, C.,He, Y.,He, B.,Cao, Y.,Dong, H.,Li, J.,Zhao, Q.,Liu, Q.,Lu, G.
Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses.
Plos Pathog., 19:e1011694-e1011694, 2023

PubMed Abstract: Alongshan virus (ALSV), a newly discovered member of unclassified Flaviviridae family, is able to infect humans. ALSV has a multi-segmented genome organization and is evolutionarily distant from canonical mono-segmented flaviviruses. The virus-encoded methyltransferase (MTase) plays an important role in viral replication. Here we show that ALSV MTase readily binds S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) but exhibits significantly lower affinities than canonical flaviviral MTases. Structures of ALSV MTase in the free and SAM/SAH-bound forms reveal that the viral enzyme possesses a unique loop-element lining side-wall of the SAM/SAH-binding pocket. While the equivalent loop in flaviviral MTases half-covers SAM/SAH, contributing multiple hydrogen-bond interactions; the pocket-lining loop of ALSV MTase is of short-length and high-flexibility, devoid of any physical contacts with SAM/SAH. Subsequent mutagenesis data further corroborate such structural difference affecting SAM/SAH-binding. Finally, we also report the structure of ALSV MTase bound with sinefungin, an SAM-analogue MTase inhibitor. These data have delineated the basis for the low-affinity interaction between ALSV MTase and SAM/SAH and should inform on antiviral drug design.

PubMed: 37831643
DOI: 10.1371/journal.ppat.1011694

実験手法

X-RAY DIFFRACTION (2.005 Å)