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| | ==Post-catalytic complex of human Polymerase Mu (G433S) mutant with incoming dTTP== | | ==Post-catalytic complex of human Polymerase Mu (G433S) mutant with incoming dTTP== |
| - | <StructureSection load='5vzc' size='340' side='right' caption='[[5vzc]], [[Resolution|resolution]] 1.55Å' scene=''> | + | <StructureSection load='5vzc' size='340' side='right'caption='[[5vzc]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vzc]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VZC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vzc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VZC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</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]] 1.552Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5twp|5twp]], [[5twq|5twq]], [[5twr|5twr]], [[5tws|5tws]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=5vzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vzc OCA], [https://pdbe.org/5vzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vzc RCSB], [https://www.ebi.ac.uk/pdbsum/5vzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vzc ProSAT]</span></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=5vzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vzc OCA], [http://pdbe.org/5vzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vzc RCSB], [http://www.ebi.ac.uk/pdbsum/5vzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vzc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN]] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</ref> | + | [https://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</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 5vzc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5vzc" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed DNA polymerase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bebenek, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Kunkel, T A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Moon, A F]] | + | [[Category: Bebenek K]] |
| - | [[Category: Pedersen, L C]] | + | [[Category: Kunkel TA]] |
| - | [[Category: Pryor, J M]] | + | [[Category: Moon AF]] |
| - | [[Category: Ramsden, D A]] | + | [[Category: Pedersen LC]] |
| - | [[Category: Dna double strand break repair]] | + | [[Category: Pryor JM]] |
| - | [[Category: Family x]] | + | [[Category: Ramsden DA]] |
| - | [[Category: Nonhomologous end-joining]]
| + | |
| - | [[Category: Ribonucleotide incorporation]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| Structural highlights
5vzc is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.552Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
DPOLM_HUMAN Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.[1] [2] [3] [4]
Publication Abstract from PubMed
While most DNA polymerases discriminate against ribonucleotide triphosphate (rNTP) incorporation very effectively, the Family X member DNA polymerase mu (Pol mu) incorporates rNTPs almost as efficiently as deoxyribonucleotides. To gain insight into how this occurs, here we have used X-ray crystallography to describe the structures of pre- and post-catalytic complexes of Pol mu with a ribonucleotide bound at the active site. These structures reveal that Pol mu binds and incorporates a rNTP with normal active site geometry and no distortion of the DNA substrate or nucleotide. Moreover, a comparison of rNTP incorporation kinetics by wildtype and mutant Pol mu indicates that rNTP accommodation involves synergistic interactions with multiple active site residues not found in polymerases with greater discrimination. Together, the results are consistent with the hypothesis that rNTP incorporation by Pol mu is advantageous in gap-filling synthesis during DNA double strand break repair by nonhomologous end joining, particularly in nonreplicating cells containing very low deoxyribonucleotide concentrations.
Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.,Moon AF, Pryor JM, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC Nucleic Acids Res. 2017 Sep 6;45(15):9138-9148. doi: 10.1093/nar/gkx527. PMID:28911097[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nick McElhinny SA, Ramsden DA. Polymerase mu is a DNA-directed DNA/RNA polymerase. Mol Cell Biol. 2003 Apr;23(7):2309-15. PMID:12640116
- ↑ Ruiz JF, Juarez R, Garcia-Diaz M, Terrados G, Picher AJ, Gonzalez-Barrera S, Fernandez de Henestrosa AR, Blanco L. Lack of sugar discrimination by human Pol mu requires a single glycine residue. Nucleic Acids Res. 2003 Aug 1;31(15):4441-9. PMID:12888504
- ↑ Capp JP, Boudsocq F, Besnard AG, Lopez BS, Cazaux C, Hoffmann JS, Canitrot Y. Involvement of DNA polymerase mu in the repair of a specific subset of DNA double-strand breaks in mammalian cells. Nucleic Acids Res. 2007;35(11):3551-60. Epub 2007 May 5. PMID:17483519 doi:http://dx.doi.org/10.1093/nar/gkm243
- ↑ DeRose EF, Clarkson MW, Gilmore SA, Galban CJ, Tripathy A, Havener JM, Mueller GA, Ramsden DA, London RE, Lee AL. Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining. Biochemistry. 2007 Oct 30;46(43):12100-10. Epub 2007 Oct 4. PMID:17915942 doi:10.1021/bi7007728
- ↑ Moon AF, Pryor JM, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC. Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu. Nucleic Acids Res. 2017 Sep 6;45(15):9138-9148. doi: 10.1093/nar/gkx527. PMID:28911097 doi:http://dx.doi.org/10.1093/nar/gkx527
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