7N7I

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

Summary for 7N7I

• Entry DOI: 10.2210/pdb7n7i/pdb
• Descriptor: Viperin-like enzyme, S-ADENOSYLMETHIONINE, IRON/SULFUR CLUSTER, ... (4 entities in total)
• Functional Keywords: radical sam protein, metalloprotein, antiviral, ddh-synthase, antiviral protein
• Biological source: Hypocrea virens (strain Gv29-8 / FGSC 10586) (Gliocladium virens, Trichoderma virens)
• Total number of polymer chains: 3
• Total formula weight: 117095.45

Authors

Grove, T.L.,Almo, S.C.,Bonanno, J.B.,Lachowicz, J.C.,Gizzi, A.G. (deposition date: 2021-06-10, release date: 2021-06-30, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.19 Å)