4glw

<StructureSection load='4glw' size='340' side='right' caption='[[4glw]], [[Resolution|resolution]] 2.00&Aring;' scene=''>

<table><tr><td colspan='2'>[[4glw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae_p1031 Streptococcus pneumoniae p1031]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GLW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GLW FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0XT:7-METHOXY-6-METHYLPTERIDINE-2,4-DIAMINE'>0XT</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3baa|3baa]], [[4glx|4glx]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ligA, SPP_1122 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=488223 Streptococcus pneumoniae P1031])</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=4glw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4glw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4glw RCSB], [http://www.ebi.ac.uk/pdbsum/4glw PDBsum]</span></td></tr>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent inhibition of bacterial NAD(+)-dependent DNA ligases (LigAs) evolved from a 2,4-diaminopteridine derivative discovered by HTS. The design was guided by several highly resolved X-ray structures of our inhibitors in complex with either Streptococcus pneumoniae or Escherichia coli LigA. The structure-activity-relationship based on the ANC scaffold is discussed. The in-depth characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1mg/L) and in vivo anti-staphylococcal activity, is presented.

 

Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity.,Surivet JP, Lange R, Hubschwerlen C, Keck W, Specklin JL, Ritz D, Bur D, Locher H, Seiler P, Strasser DS, Prade L, Kohl C, Schmitt C, Chapoux G, Ilhan E, Ekambaram N, Athanasiou A, Knezevic A, Sabato D, Chambovey A, Gaertner M, Enderlin M, Boehme M, Sippel V, Wyss P Bioorg Med Chem Lett. 2012 Sep 4. pii: S0960-894X(12)01105-5. doi:, 10.1016/j.bmcl.2012.08.094. PMID:23006603<ref>PMID:23006603</ref>

 

*[[DNA ligase|DNA ligase]]

[[Category: Streptococcus pneumoniae p1031]]

[[Category: Chambovey, A]]

[[Category: Lange, R]]

[[Category: Prade, L]]

[[Category: Tidten-Luksch, N]]

[[Category: Ligase-ligase inhibitor complex]]