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| | ==DNA ligase A in complex with inhibitor== | | ==DNA ligase A in complex with inhibitor== |
| - | <StructureSection load='4glx' size='340' side='right' caption='[[4glx]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4glx' size='340' side='right'caption='[[4glx]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4glx]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GLX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4glx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] 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=4GLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GLX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0XS:2-AMINO-6-BROMO-7-(TRIFLUOROMETHYL)-1,8-NAPHTHYRIDINE-3-CARBOXAMIDE'>0XS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0XS:2-AMINO-6-BROMO-7-(TRIFLUOROMETHYL)-1,8-NAPHTHYRIDINE-3-CARBOXAMIDE'>0XS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3baa|3baa]], [[4glw|4glw]]</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=4glx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4glx OCA], [https://pdbe.org/4glx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4glx RCSB], [https://www.ebi.ac.uk/pdbsum/4glx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4glx ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b2411, dnaL, JW2403, lig, ligA, lop, pdeC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_ligase_(NAD(+)) DNA ligase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.5.1.2 6.5.1.2] </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=4glx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4glx OCA], [http://pdbe.org/4glx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4glx RCSB], [http://www.ebi.ac.uk/pdbsum/4glx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4glx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DNLJ_ECOLI DNLJ_ECOLI]] DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.[HAMAP-Rule:MF_01588] | + | [https://www.uniprot.org/uniprot/DNLJ_ECOLI DNLJ_ECOLI] DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.[HAMAP-Rule:MF_01588] |
| | <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 4glx" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4glx" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA ligase 3D structures|DNA ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Chambovey, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Lange, R]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Prade, L]] | + | [[Category: Chambovey A]] |
| - | [[Category: Tidten-Luksch, N]] | + | [[Category: Lange R]] |
| - | [[Category: Dna ligase some]] | + | [[Category: Prade L]] |
| - | [[Category: Inhibitor]] | + | [[Category: Tidten-Luksch N]] |
| - | [[Category: Ligase-ligase inhibitor-dna complex]]
| + | |
| Structural highlights
Function
DNLJ_ECOLI DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.[HAMAP-Rule:MF_01588]
Publication Abstract from PubMed
A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent inhibition of bacterial NAD(+)-dependent DNA ligases (LigAs) evolved from a 2,4-diaminopteridine derivative discovered by HTS. The design was guided by several highly resolved X-ray structures of our inhibitors in complex with either Streptococcus pneumoniae or Escherichia coli LigA. The structure-activity-relationship based on the ANC scaffold is discussed. The in-depth characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1mg/L) and in vivo anti-staphylococcal activity, is presented.
Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity.,Surivet JP, Lange R, Hubschwerlen C, Keck W, Specklin JL, Ritz D, Bur D, Locher H, Seiler P, Strasser DS, Prade L, Kohl C, Schmitt C, Chapoux G, Ilhan E, Ekambaram N, Athanasiou A, Knezevic A, Sabato D, Chambovey A, Gaertner M, Enderlin M, Boehme M, Sippel V, Wyss P Bioorg Med Chem Lett. 2012 Sep 4. pii: S0960-894X(12)01105-5. doi:, 10.1016/j.bmcl.2012.08.094. PMID:23006603[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Surivet JP, Lange R, Hubschwerlen C, Keck W, Specklin JL, Ritz D, Bur D, Locher H, Seiler P, Strasser DS, Prade L, Kohl C, Schmitt C, Chapoux G, Ilhan E, Ekambaram N, Athanasiou A, Knezevic A, Sabato D, Chambovey A, Gaertner M, Enderlin M, Boehme M, Sippel V, Wyss P. Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity. Bioorg Med Chem Lett. 2012 Sep 4. pii: S0960-894X(12)01105-5. doi:, 10.1016/j.bmcl.2012.08.094. PMID:23006603 doi:http://dx.doi.org/10.1016/j.bmcl.2012.08.094
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