Mondal Sudipa, Reddy Subba, Mukhopadhyay Sudit S
Department of Biotechnology, National Institute of Technology, Durgapur, India.
J Biomol Struct Dyn. 2022;40(19):9374-9388. doi: 10.1080/07391102.2021.1929490. Epub 2021 May 20.
Fanconi anaemia pathway repairs inter-strand cross linking damage (ICL) of the DNA. Monoubiquitination of FANCD2 and FANCI is very crucial for ICL repairing. In this work we have tried to understand the monoubiquitinated FANCD2 structure, which facilitates the FANCD2 for binding the damage part of the chromatin. Crystal structure of the monoubiquitinated FANCD2 alone is not available, therefore we have modelled the optimized structure of the human monoubiquitinated (Lys 561) FANCD2. As there is no suitable software or web server we have developed a method for building up monoubiquitinated product and validated on simplest monoubiquitinated protein, diubiquitin. We have predicted the structure of human monoubiquitinated FANCD2 by using our method and studied the interaction with DNA by docking studies. Molecular Dynamics (MD) simulation has been used to understand the stability of the structure. Large structural differences have been observed between FANCD2 and monoubiquitinated FANCD2. Docking studies with DNA suggest that the binding site varies for the FANCD2 and monoubiquitinated FANCD2.Communicated by Ramaswamy H. Sarma.
范可尼贫血通路可修复DNA的链间交联损伤（ICL）。FANCD2和FANCI的单泛素化对于ICL修复至关重要。在这项工作中，我们试图了解单泛素化的FANCD2结构，该结构有助于FANCD2结合染色质的损伤部分。单泛素化的FANCD2的晶体结构尚无可用信息，因此我们对人单泛素化（赖氨酸561）FANCD2的优化结构进行了建模。由于没有合适的软件或网络服务器，我们开发了一种构建单泛素化产物的方法，并在最简单的单泛素化蛋白双泛素上进行了验证。我们使用我们的方法预测了人单泛素化FANCD2的结构，并通过对接研究研究了其与DNA的相互作用。分子动力学（MD）模拟已用于了解该结构的稳定性。已观察到FANCD2和单泛素化FANCD2之间存在较大的结构差异。与DNA的对接研究表明，FANCD2和单泛素化FANCD2的结合位点不同。由拉马斯瓦米·H·萨尔马传达。
