4lh7: Difference between revisions
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<StructureSection load='4lh7' size='340' side='right'caption='[[4lh7]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4lh7' size='340' side='right'caption='[[4lh7]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4lh7]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4lh7]] 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=4LH7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LH7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1X8:4-AMINOTHIENO[3,2-C]PYRIDINE-2,7-DICARBOXAMIDE'>1X8</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1X8:4-AMINOTHIENO[3,2-C]PYRIDINE-2,7-DICARBOXAMIDE'>1X8</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=4lh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lh7 OCA], [https://pdbe.org/4lh7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lh7 RCSB], [https://www.ebi.ac.uk/pdbsum/4lh7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lh7 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Enterococcus faecalis V583]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Boriack-Sjodin | [[Category: Boriack-Sjodin PA]] | ||
[[Category: Prince | [[Category: Prince DB]] | ||
Revision as of 14:01, 14 December 2022
Crystal structure of a LigA inhibitorCrystal structure of a LigA inhibitor
Structural highlights
FunctionDNLJ_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). Publication Abstract from PubMedIn 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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