4LND

Crystal structure of human apurinic/apyrimidinic endonuclease 1 with essential Mg2+ cofactor

4LND の概要

• エントリーDOI: 10.2210/pdb4lnd/pdb
• 分子名称: DNA-(apurinic or apyrimidinic site) lyase, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: apurinic/apyrimidinic endonuclease, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus. DNA-(apurinic or apyrimidinic site) lyase, mitochondrial: Mitochondrion: P27695
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 96374.39

構造登録者

Manvilla, B.A.,Pozharski, E.,Toth, E.A.,Drohat, A.C. (登録日: 2013-07-11, 公開日: 2013-11-27, 最終更新日: 2023-09-20)

主引用文献

Manvilla, B.A.,Pozharski, E.,Toth, E.A.,Drohat, A.C.
Structure of human apurinic/apyrimidinic endonuclease 1 with the essential Mg(2+) cofactor.
Acta Crystallogr.,Sect.D, 69:2555-2562, 2013

PubMed Abstract: Apurinic/apyrimidinic endonuclease 1 (APE1) mediates the repair of abasic sites and other DNA lesions and is essential for base-excision repair and strand-break repair pathways. APE1 hydrolyzes the phosphodiester bond at abasic sites, producing 5'-deoxyribose phosphate and the 3'-OH primer needed for repair synthesis. It also has additional repair activities, including the removal of 3'-blocking groups. APE1 is a powerful enzyme that absolutely requires Mg2+, but the stoichiometry and catalytic function of the divalent cation remain unresolved for APE1 and for other enzymes in the DNase I superfamily. Previously reported structures of DNA-free APE1 contained either Sm3+ or Pb2+ in the active site. However, these are poor surrogates for Mg2+ because Sm3+ is not a cofactor and Pb2+ inhibits APE1, and their coordination geometry is expected to differ from that of Mg2+. A crystal structure of human APE1 was solved at 1.92 Å resolution with a single Mg2+ ion in the active site. The structure reveals ideal octahedral coordination of Mg2+ via two carboxylate groups and four water molecules. One residue that coordinates Mg2+ directly and two that bind inner-sphere water molecules are strictly conserved in the DNase I superfamily. This structure, together with a recent structure of the enzyme-product complex, inform on the stoichiometry and the role of Mg2+ in APE1-catalyzed reactions.

PubMed: 24311596
DOI: 10.1107/S0907444913027042

実験手法

X-RAY DIFFRACTION (1.92 Å)