title: Structural basis of Zika virus methyltransferase inhibition by sinefungin.
abstract: Zika virus is considered a major global threat to human kind. Here, we present a crystal structure of one of its essential enzymes, the methyltransferase, with the inhibitor sinefungin. This structure, together with previously solved structures with bound substrates, will provide the information needed for rational inhibitor design. Based on the structural data we suggest the modification of the adenine moiety of sinefungin to increase selectivity and to covalently link it to a GTP analogue, to increase the affinity of the synthesized compounds.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Hercik
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Brynda
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic. nencka@uochb.cas.cz.
authors.forename: Radim
authors.initials: R
authors.lastname: Nencka
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic. boura@uochb.cas.cz.
authors.forename: Evzen
authors.identifier: http://orcid.org/0000-0002-9652-4065
authors.initials: E
authors.lastname: Boura
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011485:Protein Binding; D000071244:Zika Virus / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D008780:Methyltransferases; D000241:Adenosine; C006235:sinefungin