噬藻体 PBCV-1 多功能脱氨酶的结构基础。

Structural basis of a multi-functional deaminase in chlorovirus PBCV-1.

机构信息

Multidiscipline Research Center, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai, 200032, China.

出版信息

Arch Biochem Biophys. 2022 Sep 30;727:109339. doi: 10.1016/j.abb.2022.109339. Epub 2022 Jun 25.

DOI:10.1016/j.abb.2022.109339

PMID:35764100

Abstract

2-Deoxycytidylate deaminase (dCD) is a member of the zinc-dependent cytidine deaminase family features in its allosterically regulated mechanism by dCTP and dTTP. The large double-stranded DNA-containing chlorovirus PBCV-1 encodes a dCD family enzyme PBCV1dCD that was reported to be able to deaminize both dCMP and dCTP, which makes PBCV1dCD unique in the dCD family proteins. In this study, we report the crystal structure of PBCV1dCD in complex with dCTP/dCMP and dTTP/dTMP, respectively. We further proved the ability of PBCV1dCD in the deamination of dCDP, which makes PBCV1dCD a multi-functional deaminase. The structural basis for the versatility of PBCV1dCD is analyzed and discussed, with the finding of a unique Trp121 residue key to the deamination and substrate binding ability. Our findings may broaden the understanding of dCD family proteins and provide novel insights into the multi-functional enzyme.

摘要

2-脱氧胞苷脱氨酶（dCD）是锌依赖性胞苷脱氨酶家族的一员，其变构调节机制的特征在于 dCTP 和 dTTP。含有大量双链 DNA 的噬菌体 PBCV-1 编码了一种 dCD 家族酶 PBCV1dCD，据报道，它能够脱氨化 dCMP 和 dCTP，这使得 PBCV1dCD 在 dCD 家族蛋白中具有独特性。在这项研究中，我们报告了 PBCV1dCD 分别与 dCTP/dCMP 和 dTTP/dTMP 复合物的晶体结构。我们进一步证明了 PBCV1dCD 具有脱氨化 dCDP 的能力，这使得 PBCV1dCD 成为一种多功能脱氨酶。分析和讨论了 PBCV1dCD 多功能性的结构基础，发现了一个独特的色氨酸 121 残基，它是脱氨和底物结合能力的关键。我们的发现可能会拓宽对 dCD 家族蛋白的理解，并为多功能酶提供新的见解。