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4lh7

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Revision as of 11:01, 14 December 2022

Crystal structure of a LigA inhibitor

Structural highlights

4lh7 is a 1 chain structure with sequence from Enterococcus faecalis V583. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).

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.

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.

References

↑ Murphy-Benenato K, Wang H, McGuire HM, Davis HE, Gao N, Prince DB, Jahic H, Stokes SS, Boriack-Sjodin PA. Identification through structure-based methods of a bacterial NAD-dependent DNA ligase inhibitor that avoids known resistance mutations. Bioorg Med Chem Lett. 2013 Nov 15. pii: S0960-894X(13)01286-9. doi:, 10.1016/j.bmcl.2013.11.007. PMID:24287382 doi:http://dx.doi.org/10.1016/j.bmcl.2013.11.007

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lh7"

Categories: Enterococcus faecalis V583 | Large Structures | Boriack-Sjodin PA | Prince DB

@@ Line 3: / Line 3: @@
 <StructureSection load='4lh7' size='340' side='right'caption='[[4lh7]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4lh7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Entfa Entfa]. 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 [http://proteopedia.org/fgij/fg.htm?mol=4LH7 FirstGlance]. <br>
+<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>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4lh6|4lh6]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EF_0722, ligA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=226185 ENTFA])</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://proteopedia.org/fgij/fg.htm?mol=4lh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lh7 OCA], [http://pdbe.org/4lh7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lh7 RCSB], [http://www.ebi.ac.uk/pdbsum/4lh7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lh7 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 ==
@@ Line 28: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Entfa]]
+[[Category: Enterococcus faecalis V583]]
 [[Category: Large Structures]]
-[[Category: Boriack-Sjodin, P A]]
+[[Category: Boriack-Sjodin PA]]
-[[Category: Prince, D B]]
+[[Category: Prince DB]]
-[[Category: Ligase-ligase inhibitor complex]]
-[[Category: Protein-inhibitor complex]]

4lh7

From Proteopedia

Revision as of 11:01, 14 December 2022

Crystal structure of a LigA inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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