Gwangju Institute of Science and Technology(GIST·Director-General Kim Ki-sun)said on the 10th that Lee Kwang-rok, a professor at the Department of Life Sciences, provides a single amino acid residue(polypeptide) level of the principle of the operation of two active crystals of AP nucleic acid degradation enzymes that play a key function in the DNA damage repair process, and provides a short start in the development of new drugs, such as cancer treatment.
AP nucleic acid degradation enzyme is one of the most noted enzymes in cancer treatment. This enzyme mutation has been found in many cancer patients and is overexpressed early in cancer and used as a biomarker for early cancer discovery.
The research team used AP nucleic acid decomposition enzyme site-specific mutation induction method and single molecule fluorescence resonance energy transition(FRET) observation technology to reveal the fundamental mechanism of AP inner nucleic acid decomposition activity and outer nucleic acid decomposition activity at the molecular level.
This confirmed that the AP nucleic acid degradation enzyme 213th tryptophan and 213th phenylalanine has AP internucleic acid degradation activity through π-interaction with the AP spot. In addition, the 213th phenylalanine not only participates in AP inner nucleic acid degradation activity, but also stabilizes the dissociated DNA 3 end to maintain the structure that the outer nucleic acid degradation activity catalyst can occur.
The researchers demonstrated that the 90th arginine, 109th tyrosine, 121st lysine and 153rd asparagine residues of the enzyme must interact with the phosphate group of DNA to stabilize the DNA helix structure in order to exhibit external nucleic acid degradation activity.
“This study reveals the fundamental mechanisms of external and internal DNA cutting principles, two key cutting functions essential for DNA damage repair,”said Professor Kwang-rok Lee, “and is expected to contribute to the development of new drugs for cancer treatment, aging suppression, and genetic diseases in the future.”
This research was conducted by the professor’s team with the support of the Korea Research Foundation’s mid-level researcher Support project and the Basic Research Lab and JIST’s Researcher(GRI) support. The related paper was published online in the world journal “Nucleic Acid Research,” the top 2.6% paper in biochemistry&molecular biology.
Gwangju=Kim Han-sik reporter [email protected]