In DNA repair mechanism, Uracil-DNA glycosylase (UDG) is one of the most important enzymes that are involved in the process of base excision repair (BER), the function of UDG is to repair the uracil-induced DNA lesion by removing uracil from damaged DNA. Uracil in DNA may occur due to the cytosine deamination or deoxy uridine monophosphate (dUMP) residues misincorporation during DNA synthesis. Medical evidences haven shown that an abnormal expression of UDG is related to different types of cancer, including colorectal cancer, lung cancer, liver cancer, etc. Therefore, the research of UDG is crucial in cancer treatment and prevention, as well as other clinical activities. Here we applied multiple computational methods to study the UDG in several perspectives: Understand the stability of UDG enzyme in different pH conditions; study the differences in charge distribution between the pocket side and non-pocket side of UDG; analyze the field line distribution at the interfacial area between UDG and DNA; perform electrostatic binding forces analyses of special region of UDG (pocket area) and target DNA base (uracil); as well as investigate the charged residues on UDG binding pocket and binding interface. Our results show that it is the whole UDG binding interface rather than the UDG binding pocket area alone who provides the binding attractive force to a damaged DNA at uracil base.
This research is funded by Grant SC1GM132043 from National Institutes of Health (NIH); Grant 5U54MD007592 from the National Institutes on Minority Health and Health Disparities (NIMHD), a component of the NIH.
The residue distributions on the surface of UDG. (A) The electrostatic potential on the surface of UDG pocket side; (B) The electrostatic potential on the surface of the binding interface area; (C) The surface of UDG with the colored charged residues as shown in the legend; (D) The surface of UDG binding interface area; (E) The structure of UDG with the colored charged residues; (F) The structure of UDG binding interface area.
