4LND
Crystal structure of human apurinic/apyrimidinic endonuclease 1 with essential Mg2+ cofactor
Summary for 4LND
| Entry DOI | 10.2210/pdb4lnd/pdb |
| Descriptor | DNA-(apurinic or apyrimidinic site) lyase, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | apurinic/apyrimidinic endonuclease, lyase |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus. DNA-(apurinic or apyrimidinic site) lyase, mitochondrial: Mitochondrion: P27695 |
| Total number of polymer chains | 3 |
| Total formula weight | 96374.39 |
| Authors | Manvilla, B.A.,Pozharski, E.,Toth, E.A.,Drohat, A.C. (deposition date: 2013-07-11, release date: 2013-11-27, Last modification date: 2023-09-20) |
| Primary citation | 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 Cited by 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: 24311596DOI: 10.1107/S0907444913027042 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
Download full validation report
