School of Bioengineering, Qilu University of Technology, Jinan 250353, China; Department of Life Sciences, Chung-Ang University, Seoul 06974, Republic of Korea.
School of Bioengineering, Qilu University of Technology, Jinan 250353, China.
Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt A):2922-2933. doi: 10.1016/j.bbagen.2017.08.019. Epub 2017 Aug 25.
The 2-oxoglutarate/Fe(II)-dependent oxygenase (2OG oxygenase) superfamily in Metazoa is responsible for protein modification, nucleic acid repair and/or modification, and fatty acid metabolism.
Phylogenetic analysis, protein sequence similarity network (SSN) and other bioinformatics tools were used to analyze the evolutionary relationship and make functional inferences of Metazoa 2OG oxygenases.
Sixty-four 2OG oxygenases have been previously found in Homo sapiens; they catalyze two reactions: hydroxylation and demethylation. Phylogenetic analyses indicated that enzymes with similar domain architecture are always clustered together, and the redox function can be performed by the 2OG oxygenase domain or Jumonji C (JmjC) domain, where the JmjC domain is always fused to other functional domains. We used the SSN to make functional inferences and to conduct distribution analysis of Metazoa 2OG oxygenases. >11,000 putative 2OG oxygenases across Metazoa could be assigned potential functions based on the SSN. The multiple sequence alignments showed that the residues binding iron are most highly conserved in both the 2OG oxygenase domain and JmjC domain. In contrast, the residues binding oxoglutarate are quite different in the two domains: the 2OG oxygenase domain tends to have an Arg/Lys at the C terminus, whereas the JmjC domain, an Asn/Lys residue in the middle region.
The results indicated that gene duplication and vertical gene transfer have played important roles in 2OG oxygenase evolution in Metazoa and clarified the difference between the 2OG oxygenase domain and JmjC domain.
These findings expand the understanding of the diversity, evolution, and functions of 2OG oxygenases.
后生动物的 2-氧戊二酸/Fe(II)-依赖性加氧酶（2OG 加氧酶）超家族负责蛋白质修饰、核酸修复和/或修饰以及脂肪酸代谢。
使用系统发育分析、蛋白质序列相似性网络（SSN）和其他生物信息学工具来分析后生动物 2OG 加氧酶的进化关系并进行功能推断。
此前在智人中已发现 64 种 2OG 加氧酶；它们催化两种反应：羟化和去甲基化。系统发育分析表明，具有相似结构域的酶总是聚集在一起，并且氧化还原功能可以由 2OG 加氧酶结构域或 Jumonji C（JmjC）结构域执行，其中 JmjC 结构域总是与其他功能结构域融合。我们使用 SSN 进行功能推断并对后生动物 2OG 加氧酶的分布进行分析。根据 SSN，可对 >11,000 种后生动物的推定 2OG 加氧酶进行潜在功能分配。多重序列比对表明，铁结合残基在 2OG 加氧酶结构域和 JmjC 结构域中高度保守。相比之下，结合氧戊二酸的残基在两个结构域中差异很大：2OG 加氧酶结构域在 C 末端倾向于具有 Arg/Lys，而 JmjC 结构域在中间区域具有 Asn/Lys 残基。
这些结果表明，基因复制和垂直基因转移在后生动物 2OG 加氧酶进化中发挥了重要作用，并阐明了 2OG 加氧酶结构域和 JmjC 结构域之间的差异。
这些发现扩展了对 2OG 加氧酶多样性、进化和功能的理解。
