4lh6: Difference between revisions
No edit summary |
No edit summary |
||
| 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]] 1.65Å' scene=''> | <StructureSection load='4lh6' size='340' side='right' caption='[[4lh6]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
| Line 7: | Line 8: | ||
<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='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='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='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> | <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://pdbe.org/4lh6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lh6 RCSB], [http://www.ebi.ac.uk/pdbsum/4lh6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lh6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 19: | Line 20: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4lh6" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 23:36, 5 August 2016
Crystal structure of a LigA inhibitorCrystal structure of a LigA inhibitor
Structural highlights
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 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
|
| ||||||||||||||||||||||