化学
核苷酸
核苷酸
胞苷
立体化学
部分
尿苷
选择性
基质(水族馆)
酶
生物化学
核糖核酸
催化作用
基因
生物
生态学
作者
Michael K. Fenwick,Dan Su,Min Dong,Hening Lin,S.E. Ealick
出处
期刊:Biochemistry
[American Chemical Society]
日期:2020-01-09
卷期号:59 (5): 652-662
被引量:27
标识
DOI:10.1021/acs.biochem.9b00741
摘要
Viperin is a radical S-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, kcat is similar for CTP and UTP whereas the Km 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.
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