This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


4lh6

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:19, 1 March 2024) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Crystal structure of a LigA inhibitor==
==Crystal structure of a LigA inhibitor==
-
<StructureSection load='4lh6' size='340' side='right' caption='[[4lh6]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+
<StructureSection load='4lh6' size='340' side='right'caption='[[4lh6]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4lh6]] 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=4LH6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/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"><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]] 1.65&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lh7|4lh7]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ligA, EF_0722 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=226185 ENTFA])</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='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=4lh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lh6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lh6 RCSB], [http://www.ebi.ac.uk/pdbsum/4lh6 PDBsum]</span></td></tr>
+
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[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).
-
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<ref>PMID:24287382</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
==See Also==
==See Also==
-
*[[DNA ligase|DNA ligase]]
+
*[[DNA ligase 3D structures|DNA ligase 3D structures]]
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Entfa]]
+
[[Category: Enterococcus faecalis V583]]
-
[[Category: Benenato, K]]
+
[[Category: Large Structures]]
-
[[Category: Boriack-Sjodin, P A]]
+
[[Category: Benenato K]]
-
[[Category: Davis, H]]
+
[[Category: Boriack-Sjodin PA]]
-
[[Category: Gao, N]]
+
[[Category: Davis H]]
-
[[Category: Jahic, H]]
+
[[Category: Gao N]]
-
[[Category: Mcguire, H M]]
+
[[Category: Jahic H]]
-
[[Category: Prince, D B]]
+
[[Category: Mcguire HM]]
-
[[Category: Stokes, S S]]
+
[[Category: Prince DB]]
-
[[Category: Wang, H]]
+
[[Category: Stokes SS]]
-
[[Category: Ligase-ligase inhibitor complex]]
+
[[Category: Wang H]]
-
[[Category: Protein-inhibitor complex]]
+

Current revision

Crystal structure of a LigA inhibitor

PDB ID 4lh6

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lh6"
Personal tools