2lj6
From Proteopedia
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==Solution Structure and DNA-binding Properties of the Phosphoesterase Domain of DNA Ligase D== | ==Solution Structure and DNA-binding Properties of the Phosphoesterase Domain of DNA Ligase D== | ||
| - | <StructureSection load='2lj6' size='340' side='right' caption='[[2lj6 | + | <StructureSection load='2lj6' size='340' side='right'caption='[[2lj6]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[2lj6]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2lj6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LJ6 FirstGlance]. <br> |
| - | <b> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lj6 OCA], [https://pdbe.org/2lj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lj6 RCSB], [https://www.ebi.ac.uk/pdbsum/2lj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lj6 ProSAT]</span></td></tr> |
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LIGD_PSEAE LIGD_PSEAE] With Ku probably forms a non-homologous end joining (NHEJ) repair enzyme, which repairs dsDNA breaks (DSB) with reduced fidelity. Acts as a DNA ligase on singly nicked dsDNA, fills dsDNA gaps (3- or 4- nucleotide gaps, prefers a 5'-phosphate at the gap distal end, prefers dNTPs over rNTPs) (PubMed:20018881), has DNA-directed DNA polymerase activity (templated primer extension) and DNA-directed RNA polymerase activity (PubMed:15897197), adds 1 or 2 non-templated rNTP (or less well dNTP) to ssDNA or blunt-end dsDNA (primer extension). Has 3' resection activity, removing 3'-rNMPs from DNA using its 3'-ribonuclease and 3'-phosphatase activities sequentially. Resection requires a 2'-OH in the penultimate nucleoside position (i.e. a ribo- not deoxyribonucleoside) (PubMed:15897197), although the 3'-phosphatase activity does not, and its specific activity is 16-fold higher on a DNA substrate (PubMed:16046407). On appropriate substrates will extend a DNA primer to the end of the template strand and then incorporate a non-templated nucleotide.<ref>PMID:15897197</ref> <ref>PMID:16046407</ref> <ref>PMID:20018881</ref> The preference of the polymerase domain for rNTPs over dNTPs may be advantageous in quiescent cells where the dNTP pool may be limiting. | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3'-phosphomonoesterase and 3'-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE*Mn(2+)* sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primer-template duplexes with 3'-deoxynucleotide, 3'-deoxynucleotide 3'-phosphate, or 3' ribonucleotide termini reveal the surface used by PaePE to bind substrate DNA and suggest a more efficient engagement in the presence of a 3'-ribonucleotide. Spectral perturbations measured in the presence of weakly catalytic (Cd(2+)) and inhibitory (Zn(2+)) metals provide evidence for significant conformational changes at and near the active site, compared to the relatively modest changes elicited by Mn(2+). | The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3'-phosphomonoesterase and 3'-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE*Mn(2+)* sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primer-template duplexes with 3'-deoxynucleotide, 3'-deoxynucleotide 3'-phosphate, or 3' ribonucleotide termini reveal the surface used by PaePE to bind substrate DNA and suggest a more efficient engagement in the presence of a 3'-ribonucleotide. Spectral perturbations measured in the presence of weakly catalytic (Cd(2+)) and inhibitory (Zn(2+)) metals provide evidence for significant conformational changes at and near the active site, compared to the relatively modest changes elicited by Mn(2+). | ||
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Solution structure and DNA-binding properties of the phosphoesterase domain of DNA ligase D.,Natarajan A, Dutta K, Temel DB, Nair PA, Shuman S, Ghose R Nucleic Acids Res. 2012 Mar 1;40(5):2076-88. Epub 2011 Nov 13. PMID:22084199<ref>PMID:22084199</ref> | Solution structure and DNA-binding properties of the phosphoesterase domain of DNA ligase D.,Natarajan A, Dutta K, Temel DB, Nair PA, Shuman S, Ghose R Nucleic Acids Res. 2012 Mar 1;40(5):2076-88. Epub 2011 Nov 13. PMID:22084199<ref>PMID:22084199</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 2lj6" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
| - | [[Category: Dutta | + | [[Category: Dutta K]] |
| - | [[Category: Ghose | + | [[Category: Ghose R]] |
| - | [[Category: Natarajan | + | [[Category: Natarajan A]] |
| - | [[Category: Shuman | + | [[Category: Shuman S]] |
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Current revision
Solution Structure and DNA-binding Properties of the Phosphoesterase Domain of DNA Ligase D
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