6Q2P

Crystal structure of mouse viperin bound to cytidine triphosphate and S-adenosylhomocysteine

6Q2P の概要

• エントリーDOI: 10.2210/pdb6q2p/pdb
• 分子名称: Radical S-adenosyl methionine domain-containing protein 2, IRON/SULFUR CLUSTER, S-ADENOSYL-L-HOMOCYSTEINE, ... (7 entities in total)
• 機能のキーワード: interferon stimulated gene, radical s-adenosylmethionine enzyme, iron sulfur cluster, immune system
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76216.51

構造登録者

Fenwick, M.K.,Dong, M.,Lin, H.,Ealick, S.E. (登録日: 2019-08-08, 公開日: 2020-01-22, 最終更新日: 2023-10-11)

主引用文献

Fenwick, M.K.,Su, D.,Dong, M.,Lin, H.,Ealick, S.E.
Structural Basis of the Substrate Selectivity of Viperin.
Biochemistry, 59:652-662, 2020

PubMed Abstract: Viperin is a radical -adenosylmethionine (SAM) enzyme that inhibits viral replication by converting cytidine triphosphate (CTP) into 3'-deoxy-3',4'-didehydro-CTP and by additional undefined mechanisms operating through its N- and C-terminal domains. Here, we describe crystal structures of viperin bound to a SAM analogue and CTP or uridine triphosphate (UTP) and report kinetic parameters for viperin-catalyzed reactions with CTP or UTP as substrates. Viperin orients the C4' hydrogen atom of CTP and UTP similarly for abstraction by a 5'-deoxyadenosyl radical, but the uracil moiety introduces unfavorable interactions that prevent tight binding of UTP. Consistently, is similar for CTP and UTP whereas the for UTP is much greater. The structures also show that nucleotide binding results in ordering of the C-terminal tail and reveal that this region contains a P-loop that binds the γ-phosphate of the bound nucleotide. Collectively, the results explain the selectivity for CTP and reveal a structural role for the C-terminal tail in binding CTP and UTP.

PubMed: 31917549
DOI: 10.1021/acs.biochem.9b00741

実験手法

X-RAY DIFFRACTION (1.452 Å)