一项分子动力学模拟研究对与 SAH 和 RNA 类似物结合的寨卡病毒 NS5 甲基转移酶进行了解码。
A molecular dynamics simulation study decodes the Zika virus NS5 methyltransferase bound to SAH and RNA analogue.
机构信息
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
出版信息
Sci Rep. 2018 Apr 20;8(1):6336. doi: 10.1038/s41598-018-24775-4.
Since 2015, widespread Zika virus outbreaks in Central and South America have caused increases in microcephaly cases, and this acute problem requires urgent attention. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to investigate the structure of Zika NS5 protein with S-adenosyl-L-homocysteine (SAH) and an RNA analogue, namely 7-methylguanosine 5'-triphosphate (m7GTP). For the binding motif of Zika virus NS5 protein and SAH, we suggest that the four Zika NS5 substructures (residue orders: 101-112, 54-86, 127-136 and 146-161) and the residues (Ser56, Gly81, Arg84, Trp87, Thr104, Gly106, Gly107, His110, Asp146, Ile147, and Gly148) might be responsible for the selectivity of the new Zika virus drugs. For the binding motif of Zika NS5 protein and m7GTP, we suggest that the three Zika NS5 substructures (residue orders: 11-31, 146-161 and 207-218) and the residues (Asn17, Phe24, Lys28, Lys29, Ser150, Arg213, and Ser215) might be responsible for the selectivity of the new Zika virus drugs.
自 2015 年以来，中美洲和南美洲广泛爆发寨卡病毒，导致小头症病例增加，这一急性问题需要引起紧急关注。我们采用分子动力学和高斯加速分子动力学技术，研究了寨卡病毒 NS5 蛋白与 S-腺苷-L-同型半胱氨酸（SAH）和 RNA 类似物 7-甲基鸟苷 5'-三磷酸（m7GTP）的结构。对于寨卡病毒 NS5 蛋白与 SAH 的结合基序，我们提出寨卡病毒 NS5 的四个亚结构（残基顺序：101-112、54-86、127-136 和 146-161）和残基（Ser56、Gly81、Arg84、Trp87、Thr104、Gly106、Gly107、His110、Asp146、Ile147 和 Gly148）可能负责新寨卡病毒药物的选择性。对于寨卡 NS5 蛋白与 m7GTP 的结合基序，我们提出寨卡病毒 NS5 的三个亚结构（残基顺序：11-31、146-161 和 207-218）和残基（Asn17、Phe24、Lys28、Lys29、Ser150、Arg213 和 Ser215）可能负责新寨卡病毒药物的选择性。
Zotero 插件