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| | ==Crystal structure of human ALKBH7 in complex with N-oxalylglycine and Mn(II)== | | ==Crystal structure of human ALKBH7 in complex with N-oxalylglycine and Mn(II)== |
| - | <StructureSection load='4qkf' size='340' side='right' caption='[[4qkf]], [[Resolution|resolution]] 1.99Å' scene=''> | + | <StructureSection load='4qkf' size='340' side='right'caption='[[4qkf]], [[Resolution|resolution]] 1.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qkf]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QKF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qkf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QKF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qkd|4qkd]], [[4qkb|4qkb]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkf OCA], [http://pdbe.org/4qkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qkf RCSB], [http://www.ebi.ac.uk/pdbsum/4qkf PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qkf OCA], [https://pdbe.org/4qkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qkf RCSB], [https://www.ebi.ac.uk/pdbsum/4qkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qkf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ALKB7_HUMAN ALKB7_HUMAN]] Probable dioxygenase required to induce programmed necrosis in response to DNA damage caused by cytotoxic alkylating agents. Acts by triggering the collapse of mitochondrial membrane potential and loss of mitochondrial function that leads to energy depletion and cell death. ALKBH7-mediated necrosis is probably required to prevent the accumulation of cells with DNA damage. Does not display DNA demethylase activity. Involved in fatty acid metabolism.<ref>PMID:23666923</ref> | + | [https://www.uniprot.org/uniprot/ALKB7_HUMAN ALKB7_HUMAN] Probable dioxygenase required to induce programmed necrosis in response to DNA damage caused by cytotoxic alkylating agents. Acts by triggering the collapse of mitochondrial membrane potential and loss of mitochondrial function that leads to energy depletion and cell death. ALKBH7-mediated necrosis is probably required to prevent the accumulation of cells with DNA damage. Does not display DNA demethylase activity. Involved in fatty acid metabolism.<ref>PMID:23666923</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4qkf" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4qkf" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chen, Z]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Wang, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Dioxygenase]] | + | [[Category: Chen Z]] |
| - | [[Category: Fat metabolism]] | + | [[Category: Wang G]] |
| - | [[Category: Metal-binding]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Programmed necrosis]]
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| Structural highlights
Function
ALKB7_HUMAN Probable dioxygenase required to induce programmed necrosis in response to DNA damage caused by cytotoxic alkylating agents. Acts by triggering the collapse of mitochondrial membrane potential and loss of mitochondrial function that leads to energy depletion and cell death. ALKBH7-mediated necrosis is probably required to prevent the accumulation of cells with DNA damage. Does not display DNA demethylase activity. Involved in fatty acid metabolism.[1]
Publication Abstract from PubMed
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 alpha-ketoglutarate at 1.35 A or N-oxalylglycine at 2.0 A resolution. ALKBH7 possesses the conserved double-stranded beta-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 beta-strands beta6 and beta7 and between beta9 and beta10 create a special outer wall of the minor beta-sheet of the double-stranded beta-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.
The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein for programmed necrosis and fat metabolism.,Wang G, He Q, Feng C, Liu Y, Deng Z, Qi X, Wu W, Mei P, Chen Z J Biol Chem. 2014 Oct 3;289(40):27924-36. doi: 10.1074/jbc.M114.590505. Epub 2014, Aug 13. PMID:25122757[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fu D, Jordan JJ, Samson LD. Human ALKBH7 is required for alkylation and oxidation-induced programmed necrosis. Genes Dev. 2013 May 15;27(10):1089-100. doi: 10.1101/gad.215533.113. Epub 2013, May 10. PMID:23666923 doi:http://dx.doi.org/10.1101/gad.215533.113
- ↑ 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. 2014 Oct 3;289(40):27924-36. doi: 10.1074/jbc.M114.590505. Epub 2014, Aug 13. PMID:25122757 doi:http://dx.doi.org/10.1074/jbc.M114.590505
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