@article{b88ff1d0426e4e84b4e2f22b02a7ce62,
title = "APE1 distinguishes DNA substrates in exonucleolytic cleavage by induced space-filling",
abstract = "The exonuclease activity of Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for processing matched/mismatched terminus in various DNA repair pathways and for removing nucleoside analogs associated with drug resistance. To fill in the gap of structural basis for exonucleolytic cleavage, we determine the APE1-dsDNA complex structures displaying end-binding. As an exonuclease, APE1 does not show base preference but can distinguish dsDNAs with different structural features. Integration with assaying enzyme activity and binding affinity for a variety of substrates reveals for the first time that both endonucleolytic and exonucleolytic cleavage can be understood by an induced space-filling model. Binding dsDNA induces RM (Arg176 and Met269) bridge that defines a long and narrow product pocket for exquisite machinery of substrate selection. Our study paves the way to comprehend end-processing of dsDNA in the cell and the drug resistance relating to APE1.",
author = "Liu, {Tung Chang} and Lin, {Chun Ting} and Chang, {Kai Cheng} and Guo, {Kai Wei} and Shuying Wang and Chu, {Jhih Wei} and Hsiao, {Yu Yuan}",
note = "Funding Information: A portion of this research was performed at the National Synchrotron Radiation Research Center (BL-13B1, BL-13C1, and TPS-05A), a national user facility supported by the National Science Council of Taiwan, ROC. The Synchrotron Radiation Protein Crystallography Facility is supported by the National Core Facility Program for Biotechnology. This work is financially supported by the Ministry of Science and Technology (MOST) of Taiwan under grant number MOST 109-2113-M-009-023 to J.-W.C. and through the Excellent Youth Scholar Grant and Young Scholar Fellowship (Columbus) Program under grant number MOST 107-2628-B-009-001, MOST 108-2636-B-009-004, and MOST 109-2636-B-009-004 to Y.-Y.H. The financially support from the “Center For Intelligent Drug Systems and Smart Bio-devices (IDS2B)” and the “Smart Platform of Dynamic Systems Biology for Therapeutic Development” project from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan is also acknowledged. This study is supported partially by the NCTU-KMU JOINT RESEARCH PROJECT, Kaohsiung Medical University (NCTUKMU108-DR-01). Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = jan,
day = "27",
doi = "10.1038/s41467-020-20853-2",
language = "English",
volume = "12",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}