This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4gz2

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 11:02, 22 July 2020

Mus Musculus Tdp2 excluded ssDNA complex

Structural highlights

4gz2 is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4gyz, 4gz0, 4gz1
Gene:	Tdp2, Ttrap (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zeng Z, Sharma A, Ju L, Murai J, Umans L, Vermeire L, Pommier Y, Takeda S, Huylebroeck D, Caldecott KW, El-Khamisy SF. TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1. Nucleic Acids Res. 2012 Sep 1;40(17):8371-80. Epub 2012 Jun 26. PMID:22740648 doi:http://dx.doi.org/10.1093/nar/gks622
↑ Schellenberg MJ, Appel CD, Adhikari S, Robertson PD, Ramsden DA, Williams RS. Mechanism of repair of 5'-topoisomerase II-DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2. Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2418. PMID:23104055 doi:http://dx.doi.org/10.1038/nsmb.2418

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gz2"

@@ Line 1: / Line 1: @@
 ==Mus Musculus Tdp2 excluded ssDNA complex==
-<StructureSection load='4gz2' size='340' side='right' caption='[[4gz2]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+<StructureSection load='4gz2' size='340' side='right'caption='[[4gz2]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4gz2]] is a 4 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=4GZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GZ2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4gz2]] is a 4 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=4GZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4GZ2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gyz|4gyz]], [[4gz0|4gz0]], [[4gz1|4gz1]]</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=4gz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gz2 OCA], [http://pdbe.org/4gz2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gz2 RCSB], [http://www.ebi.ac.uk/pdbsum/4gz2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gz2 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4gz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gz2 OCA], [http://pdbe.org/4gz2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gz2 RCSB], [http://www.ebi.ac.uk/pdbsum/4gz2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gz2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[Phosphodiesterase|Phosphodiesterase]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Schellenberg, M J]]

4gz2

From Proteopedia

Revision as of 11:02, 22 July 2020

Mus Musculus Tdp2 excluded ssDNA complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox