6Q2P

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

Summary for 6Q2P

• Entry DOI: 10.2210/pdb6q2p/pdb
• Descriptor: Radical S-adenosyl methionine domain-containing protein 2, IRON/SULFUR CLUSTER, S-ADENOSYL-L-HOMOCYSTEINE, ... (7 entities in total)
• Functional Keywords: interferon stimulated gene, radical s-adenosylmethionine enzyme, iron sulfur cluster, immune system
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 76216.51

Authors

Fenwick, M.K.,Dong, M.,Lin, H.,Ealick, S.E. (deposition date: 2019-08-08, release date: 2020-01-22, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.452 Å)