4gz0
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Mus Musculus Tdp2-DNA Substrate Analog (5'-6-aminohexanol) Complex== | |
| + | <StructureSection load='4gz0' size='340' side='right' caption='[[4gz0]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4gz0]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GZ0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6AH:6-AMINOHEXAN-1-OL'>6AH</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gyz|4gyz]], [[4gz1|4gz1]], [[4gz2|4gz2]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tdp2, Ttrap ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4gz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gz0 OCA], [http://pdbe.org/4gz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gz0 RCSB], [http://www.ebi.ac.uk/pdbsum/4gz0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gz0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/TYDP2_MOUSE TYDP2_MOUSE]] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. Acts as a regulator of ribosome biogenesis following stress.<ref>PMID:22740648</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The topoisomerase II (topo II) DNA incision-and-ligation cycle can be poisoned (for example following treatment with cancer chemotherapeutics) to generate cytotoxic DNA double-strand breaks (DSBs) with topo II covalently conjugated to DNA. Tyrosyl-DNA phosphodiesterase 2 (Tdp2) protects genomic integrity by reversing 5'-phosphotyrosyl-linked topo II-DNA adducts. Here, X-ray structures of mouse Tdp2-DNA complexes reveal that Tdp2 beta-2-helix-beta DNA damage-binding 'grasp', helical 'cap' and DNA lesion-binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove. The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing. Structural, mutational and functional analyses support a single-metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase (EEP) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs. | ||
| - | + | Mechanism of repair of 5'-topoisomerase II-DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2.,Schellenberg MJ, Appel CD, Adhikari S, Robertson PD, Ramsden DA, Williams RS Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2418. PMID:23104055<ref>PMID:23104055</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4gz0" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Phosphodiesterase|Phosphodiesterase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Lk3 transgenic mice]] | ||
| + | [[Category: Schellenberg, M J]] | ||
| + | [[Category: Williams, R S]] | ||
| + | [[Category: 5'-dna end processing]] | ||
| + | [[Category: 5'-dna end recognition]] | ||
| + | [[Category: 5'-end recognition]] | ||
| + | [[Category: Dna repair]] | ||
| + | [[Category: Eep]] | ||
| + | [[Category: Eep domain]] | ||
| + | [[Category: Endonuclease/exonuclease/phosphatase domain]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Hydrolase-dna complex]] | ||
| + | [[Category: Nuclear]] | ||
| + | [[Category: Protein-dna complex]] | ||
Current revision
Mus Musculus Tdp2-DNA Substrate Analog (5'-6-aminohexanol) Complex
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