Research Progress in Human AP Endonuclease 1: Structure, Catalytic
Mechanism, and Inhibitors

Zelan      Zhang; Zhixiang      Wu; Xiaodong      Shi; Du      Guo; Yan      Cheng; Jiaxing      Gao; Ling      Liu; Wei      Liu; Li      Liang; Lianxin      Peng; Jianping      Hu
doi:10.2174/1389203723666220406132737
Abstract

The high stability of phosphodiester bonds is considered to be one of the important reasons for the genetic role of nucleic acids, and their cleavage is also the core of many key biochemical processes, including DNA replication/ repair, and RNA processing/ degradation. As an important part of the base excision repair (BER) pathway, human apurinic/ apyrimidinic endonuclease 1 (APE1) is indispensable for the repair of abasic sites and other DNA damage, including ionizing radiation, DNA covalently bonding induced by cytotoxic antitumor drugs, etc. For tumor cells, the DNA repair activity of APE1 may lead to the occurrence of radiotherapy and chemotherapy resistance. The overexpression of APE1 often poses a serious threat to the effectiveness of tumor treatment, indicating a longer time, a much larger dose, less effective chemotherapy, and poor prognosis. It is of great urgency to design novel APE1 inhibitors. Rational design and modification of inhibitor molecules are closely related to the research progress of both structural biology and catalytic mechanism. In this review, the structure, catalytic mechanism, inhibitors, and other important biochemical information regarding APE1 are summarized, which will help in the design and modification of drug molecules targeting APE1.
Keywords: Chemotherapy resistance, APE1, structure, catalytic mechanism, inhibitor, phosphodiester bonds.
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DOI https://dx.doi.org/10.2174/1389203723666220406132737	Print ISSN 1389-2037
Publisher Name Bentham Science Publisher	Online ISSN 1875-5550
Current Protein & Peptide Science

Research Progress in Human AP Endonuclease 1: Structure, Catalytic Mechanism, and Inhibitors

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