4QKF
Crystal structure of human ALKBH7 in complex with N-oxalylglycine and Mn(II)
Summary for 4QKF
| Entry DOI | 10.2210/pdb4qkf/pdb |
| Related | 4QKB 4QKD |
| Descriptor | Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial, MANGANESE (II) ION, N-OXALYLGLYCINE, ... (4 entities in total) |
| Functional Keywords | dioxygenase, metal-binding, oxidoreductase, programmed necrosis, fat metabolism |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion matrix : Q9BT30 |
| Total number of polymer chains | 3 |
| Total formula weight | 68246.74 |
| Authors | |
| Primary citation | Wang, G.,He, Q.,Feng, C.,Liu, Y.,Deng, Z.,Qi, X.,Wu, W.,Mei, P.,Chen, Z. The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein for programmed necrosis and fat metabolism J.Biol.Chem., 289:27924-27936, 2014 Cited by PubMed Abstract: ALKBH7 is the mitochondrial AlkB family member that is required for alkylation- and oxidation-induced programmed necrosis. In contrast to the protective role of other AlkB family members after suffering alkylation-induced DNA damage, ALKBH7 triggers the collapse of mitochondrial membrane potential and promotes cell death. Moreover, genetic ablation of mouse Alkbh7 dramatically increases body weight and fat mass. Here, we present crystal structures of human ALKBH7 in complex with Mn(II) and α-ketoglutarate at 1.35 Å or N-oxalylglycine at 2.0 Å resolution. ALKBH7 possesses the conserved double-stranded β-helix fold that coordinates a catalytically active iron by a conserved HX(D/E) … Xn … H motif. Self-hydroxylation of Leu-110 was observed, indicating that ALKBH7 has the potential to catalyze hydroxylation of its substrate. Unlike other AlkB family members whose substrates are DNA or RNA, ALKBH7 is devoid of the "nucleotide recognition lid" which is essential for binding nucleobases, and thus exhibits a solvent-exposed active site; two loops between β-strands β6 and β7 and between β9 and β10 create a special outer wall of the minor β-sheet of the double-stranded β-helix and form a negatively charged groove. These distinct features suggest that ALKBH7 may act on protein substrate rather than nucleic acids. Taken together, our findings provide a structural basis for understanding the distinct function of ALKBH7 in the AlkB family and offer a foundation for drug design in treating cell death-related diseases and metabolic diseases. PubMed: 25122757DOI: 10.1074/jbc.M114.590505 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.99 Å) |
Structure validation
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