Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia, India.
Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India.
J Biomol Struct Dyn. 2021 May;39(8):2771-2787. doi: 10.1080/07391102.2020.1754914. Epub 2020 May 6.
The gamma-proteobacteria DSM 180 () encodes the sulfur oxidizing operon comprising of 15 genes. Dsr proteins are involved in oxidation of sulfur globules produced as an obligatory intermediate during the sulfur oxidation process. The and gene products are known to function as a αβ hetero-tetramer and the protein complex plays the catalytic role in sulfur oxidation process. DsrC has a highly conserved C-terminal domain that forms a flexible arm, where two strictly conserved cysteines were found to act as a substrate donating residue for DsrAB instead of being a subunit of this redox enzyme. Therefore, to elucidate the molecular mechanism of the sulfur oxidation process here an attempt was made to study the dynamics, stability and binding mechanisms of DsrAB and DsrC proteins through computational docking and molecular dynamics (MD) simulations. This structure function relationship investigation revealed that the C-terminal domain of DsrC interacts with DsrA of DsrAB protein complex for catalytic functions. Some basic amino acid residues of DsrC are found to form the catalytic pockets along with DsrAB protein complex where the sulfur anions bind to get oxidized. Structural dynamics and fluctuations as well as the secondary structural alterations study revealed the possible regions responsible for protein-protein interactions. Principal Component Analysis (PCA) of protein motions displayed that the collective motions of DsrAB-DsrC complex was higher and more anti-correlated than the unbound DsrAB form. The present molecular insight study would therefore help researchers to predict the plausible biochemical mechanism of sulfur oxidation process in sulfur metabolic pathways in near future. Communicated by Ramaswamy H. Sarma.
γ-变形菌 DSM 180() 编码由 15 个基因组成的硫氧化操纵子。Dsr 蛋白参与硫氧化过程中作为必需中间产物产生的硫球的氧化。已知 和 基因产物作为一个αβ异四聚体发挥作用，该蛋白复合物在硫氧化过程中发挥催化作用。DsrC 具有高度保守的 C 末端结构域，形成一个灵活的臂，其中发现两个严格保守的半胱氨酸充当 DsrAB 的供体残基，而不是作为该氧化还原酶的亚基。因此，为了阐明硫氧化过程的分子机制，我们试图通过计算对接和分子动力学（MD）模拟研究 DsrAB 和 DsrC 蛋白的动力学、稳定性和结合机制。这项结构功能关系研究表明，DsrC 的 C 末端结构域与 DsrAB 蛋白复合物的 DsrA 相互作用以发挥催化功能。DsrC 的一些碱性氨基酸残基与 DsrAB 蛋白复合物一起形成催化口袋，硫阴离子结合在此处被氧化。结构动力学和波动以及二级结构改变研究揭示了可能负责蛋白质-蛋白质相互作用的区域。蛋白质运动的主成分分析（PCA）显示，DsrAB-DsrC 复合物的集体运动比未结合的 DsrAB 形式更高且更反相关。因此，目前的分子研究将有助于研究人员在不久的将来预测硫代谢途径中硫氧化过程的可能生化机制。由 Ramaswamy H. Sarma 传达。
