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科学家发现第三种嘌呤生物合成途径
作者:小柯机器人 发布时间:2021/4/30 22:13:16

法国巴斯德研究所Pierre Alexandre Kaminski团队发现第三种嘌呤生物合成途径。该研究于2021年4月30日发表于国际一流学术期刊《科学》。

据研究人员介绍,细胞具有两种嘌呤途径,通过肌苷从磷酸核糖合成腺嘌呤和鸟嘌呤核糖核苷酸。腺嘌呤和鸟嘌呤之间的化学混合物2-氨基腺嘌呤(Z)取代了蓝细菌病毒(S-2L)DNA中的腺嘌呤。

研究人员发现,S-2L和弧菌噬菌体PhiVC8编码由PurZ催化的第三种嘌呤途径,一种琥珀酸腺苷酸合酶(PurA)的遥远旁系同源物,该酶在腺嘌呤途径中浓缩天冬氨酸和肌醇。PurZ将天门冬氨酸与脱氧鸟苷酸缩合成dSMP(N6-succino-2-amino-2′-deoxyadenylate),然后进行去富马酰化和磷酸化,得到dZTP(2-amino-2′-deoxyadenosine-5′-triphosphate),一种噬菌体DNA聚合酶的底物。晶体学和系统发育分析表明了噬菌体PurZ和古细菌PurA酶之间的密切关系。

这项工作阐明了生物催化的新方法,其重塑了超越常规分子生物学的DNA构建基块。

附:英文原文

Title: A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes

Author: Dona Sleiman, Pierre Simon Garcia, Marion Lagune, Jerome Loc’h, Ahmed Haouz, Najwa Taib, Pascal Rthlisberger, Simonetta Gribaldo, Philippe Marlière, Pierre Alexandre Kaminski

Issue&Volume: 2021/04/30

Abstract: Cells have two purine pathways that synthesize adenine and guanine ribonucleotides from phosphoribose via inosylate. A chemical hybrid between adenine and guanine, 2-aminoadenine (Z), replaces adenine in the DNA of the cyanobacterial virus S-2L. We show that S-2L and Vibrio phage PhiVC8 encode a third purine pathway catalyzed by PurZ, a distant paralog of succinoadenylate synthase (PurA), the enzyme condensing aspartate and inosylate in the adenine pathway. PurZ condenses aspartate with deoxyguanylate into dSMP (N6-succino-2-amino-2′-deoxyadenylate), which undergoes defumarylation and phosphorylation to give dZTP (2-amino-2′-deoxyadenosine-5′-triphosphate), a substrate for the phage DNA polymerase. Crystallography and phylogenetics analyses indicate a close relationship between phage PurZ and archaeal PurA enzymes. Our work elucidates the biocatalytic innovation that remodeled a DNA building block beyond canonical molecular biology.

DOI: 10.1126/science.abe6494

Source: https://science.sciencemag.org/content/372/6541/516

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037