8PEM

Zika Methyltransferase in complex with AT-9010 and SAH

8PEM の概要

• エントリーDOI: 10.2210/pdb8pem/pdb
• 分子名称: RNA-directed RNA polymerase NS5, [[(2R,3R,4R,5R)-5-(2-azanyl-6-oxidanylidene-1H-purin-9-yl)-4-fluoranyl-4-methyl-3-oxidanyl-oxolan-2-yl]methoxy-oxidanyl-phosphoryl] phosphono hydrogen phosphate, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• 機能のキーワード: ntaya virus, methyltransferase, at-9010, sah, viral protein
• 由来する生物種: Zika virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30339.20

構造登録者

Krejcova, K.,Boura, E.,Klima, M. (登録日: 2023-06-14, 公開日: 2024-06-26, 最終更新日: 2026-01-14)

主引用文献

Krejcova, K.,Boura, E.
Structural basis for broad-spectrum binding of AT-9010 to flaviviral methyltransferases.
Arch Virol, 170:61-61, 2025

PubMed Abstract: AT-9010 (2'-methyl-2'-fluoro guanosine triphosphate) is a GTP analog whose prodrug, AT-752 is under consideration in human medicine as a potential antiviral drug against certain flaviviruses. It was previously believed to inhibit viral replication by acting primarily as a chain terminator. However, it was discovered recently that it also binds the GTP binding site of the methyltransferase (MTase) domain of the orthoflavivirus polymerase, thus interfering with RNA capping. Here, we investigated the binding of AT-9010 to Ntaya and Zika virus MTases. Structural analysis using X-ray crystallography revealed similar interactions between the base and sugar moieties of AT-9010 and key residues in both MTases, although differences in hydrogen bonding were observed. Our analysis also suggested that the triphosphate part of AT-9010 is flexible. Despite minor variations, the overall binding mode of AT-9010 was found to be the same for all of the flaviviral MTases examined, suggesting a structural basis for the efficacy of AT-9010 against multiple orthoflavivirus MTases.

PubMed: 39976734
DOI: 10.1007/s00705-025-06227-3

実験手法

X-RAY DIFFRACTION (2 Å)