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| | ==DNA ligase A in complex with inhibitor== | | ==DNA ligase A in complex with inhibitor== |
| - | <StructureSection load='4glw' size='340' side='right' caption='[[4glw]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4glw' size='340' side='right'caption='[[4glw]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4glw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Strzp Strzp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GLW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GLW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4glw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_P1031 Streptococcus pneumoniae P1031]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GLW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0XT:7-METHOXY-6-METHYLPTERIDINE-2,4-DIAMINE'>0XT</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0XT:7-METHOXY-6-METHYLPTERIDINE-2,4-DIAMINE'>0XT</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3baa|3baa]], [[4glx|4glx]]</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=4glw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4glw OCA], [https://pdbe.org/4glw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4glw RCSB], [https://www.ebi.ac.uk/pdbsum/4glw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4glw ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ligA, SPP_1122 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=488223 STRZP])</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=4glw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4glw OCA], [http://pdbe.org/4glw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4glw RCSB], [http://www.ebi.ac.uk/pdbsum/4glw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4glw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DNLJ_STRZP DNLJ_STRZP]] 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_STRZP DNLJ_STRZP] 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 4glw" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4glw" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA ligase 3D structures|DNA ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Strzp]] | + | [[Category: Large Structures]] |
| - | [[Category: Chambovey, A]] | + | [[Category: Streptococcus pneumoniae P1031]] |
| - | [[Category: Lange, R]] | + | [[Category: Chambovey A]] |
| - | [[Category: Prade, L]] | + | [[Category: Lange R]] |
| - | [[Category: Tidten-Luksch, N]] | + | [[Category: Prade L]] |
| - | [[Category: Dna ligase some]]
| + | [[Category: Tidten-Luksch N]] |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Ligase-ligase inhibitor complex]]
| + | |
| Structural highlights
Function
DNLJ_STRZP 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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