7N7I

X-ray crystal structure of Viperin-like enzyme from Trichoderma virens

7N7I の概要

• エントリーDOI: 10.2210/pdb7n7i/pdb
• 分子名称: Viperin-like enzyme, S-ADENOSYLMETHIONINE, IRON/SULFUR CLUSTER, ... (4 entities in total)
• 機能のキーワード: radical sam protein, metalloprotein, antiviral, ddh-synthase, antiviral protein
• 由来する生物種: Hypocrea virens (strain Gv29-8 / FGSC 10586) (Gliocladium virens, Trichoderma virens)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 117095.45

構造登録者

Grove, T.L.,Almo, S.C.,Bonanno, J.B.,Lachowicz, J.C.,Gizzi, A.G. (登録日: 2021-06-10, 公開日: 2021-06-30, 最終更新日: 2023-10-18)

主引用文献

Lachowicz, J.C.,Gizzi, A.S.,Almo, S.C.,Grove, T.L.
Structural Insight into the Substrate Scope of Viperin and Viperin-like Enzymes from Three Domains of Life.
Biochemistry, 60:2116-2129, 2021

PubMed Abstract: Viperin is a member of the radical -adenosylmethionine superfamily and has been shown to restrict the replication of a wide range of RNA and DNA viruses. We recently demonstrated that human viperin (HsVip) catalyzes the conversion of CTP to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP or ddh-synthase), which acts as a chain terminator for virally encoded RNA-dependent RNA polymerases from several flaviviruses. Viperin homologues also exist in non-chordate eukaryotes (e.g., Cnidaria and Mollusca), numerous fungi, and members of the archaeal and eubacterial domains. Recently, it was reported that non-chordate and non-eukaryotic viperin-like homologues are also ddh-synthases and generate a diverse range of ddhNTPs, including the newly discovered ddhUTP and ddhGTP. Herein, we expand on the catalytic mechanism of mammalian, fungal, bacterial, and archaeal viperin-like enzymes with a combination of X-ray crystallography and enzymology. We demonstrate that, like mammalian viperins, these recently discovered viperin-like enzymes operate through the same mechanism and can be classified as ddh-synthases. Furthermore, we define the unique chemical and physical determinants supporting ddh-synthase activity and nucleotide selectivity, including the crystallographic characterization of a fungal viperin-like enzyme that utilizes UTP as a substrate and a cnidaria viperin-like enzyme that utilizes CTP as a substrate. Together, these results support the evolutionary conservation of the ddh-synthase activity and its broad phylogenetic role in innate antiviral immunity.

PubMed: 34156827
DOI: 10.1021/acs.biochem.0c00958

実験手法

X-RAY DIFFRACTION (3.19 Å)