4lh6
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4lh6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis_V583 Enterococcus faecalis V583]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LH6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4lh6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis_V583 Enterococcus faecalis V583]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LH6 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1X7:4-AMINO-2-BROMOTHIENO[3,2-C]PYRIDINE-7-CARBOXAMIDE'>1X7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</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]] 1.65Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1X7:4-AMINO-2-BROMOTHIENO[3,2-C]PYRIDINE-7-CARBOXAMIDE'>1X7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene></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=4lh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lh6 OCA], [https://pdbe.org/4lh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lh6 RCSB], [https://www.ebi.ac.uk/pdbsum/4lh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lh6 ProSAT]</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=4lh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lh6 OCA], [https://pdbe.org/4lh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lh6 RCSB], [https://www.ebi.ac.uk/pdbsum/4lh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lh6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/DNLJ_ENTFA DNLJ_ENTFA] 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 (By similarity). | [https://www.uniprot.org/uniprot/DNLJ_ENTFA DNLJ_ENTFA] 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 (By similarity). | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | In an attempt to identify novel inhibitors of NAD+-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed analysis of the binding sites of a variety of bacterial ligases was performed. This analysis revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymology revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chemistry program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-positive bacterial LigA enzymes. | ||
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| - | Identification through structure-based methods of a bacterial NAD-dependent DNA ligase inhibitor that avoids known resistance mutations.,Murphy-Benenato K, Wang H, McGuire HM, Davis HE, Gao N, Prince DB, Jahic H, Stokes SS, Boriack-Sjodin PA Bioorg Med Chem Lett. 2013 Nov 15. pii: S0960-894X(13)01286-9. doi:, 10.1016/j.bmcl.2013.11.007. PMID:24287382<ref>PMID:24287382</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4lh6" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[DNA ligase 3D structures|DNA ligase 3D structures]] | *[[DNA ligase 3D structures|DNA ligase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of a LigA inhibitor
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