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[[ | ==S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines== | ||
<StructureSection load='3srw' size='340' side='right' caption='[[3srw]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3srw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SRW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SRW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=Q27:7-(2-ETHOXYNAPHTHALEN-1-YL)-6-METHYLQUINAZOLINE-2,4-DIAMINE'>Q27</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sqy|3sqy]], [[3sr5|3sr5]], [[3srq|3srq]], [[3srr|3srr]], [[3srs|3srs]], [[3sru|3sru]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=3srw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3srw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3srw RCSB], [http://www.ebi.ac.uk/pdbsum/3srw PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains. | |||
Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.,Li X, Hilgers M, Cunningham M, Chen Z, Trzoss M, Zhang J, Kohnen L, Lam T, Creighton C, Gc K, Nelson K, Kwan B, Stidham M, Brown-Driver V, Shaw KJ, Finn J Bioorg Med Chem Lett. 2011 Sep 15;21(18):5171-6. Epub 2011 Jul 23. PMID:21831637<ref>PMID:21831637</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Dihydrofolate reductase|Dihydrofolate reductase]] | *[[Dihydrofolate reductase|Dihydrofolate reductase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Hilgers, M | [[Category: Hilgers, M]] | ||
[[Category: Dhfr]] | [[Category: Dhfr]] | ||
[[Category: Drug design]] | [[Category: Drug design]] | ||
[[Category: Enzyme inhibitor]] | [[Category: Enzyme inhibitor]] | ||
[[Category: Folate]] | [[Category: Folate]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
Revision as of 15:27, 9 December 2014
S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolinesS. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines
Structural highlights
Publication Abstract from PubMedDihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains. Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.,Li X, Hilgers M, Cunningham M, Chen Z, Trzoss M, Zhang J, Kohnen L, Lam T, Creighton C, Gc K, Nelson K, Kwan B, Stidham M, Brown-Driver V, Shaw KJ, Finn J Bioorg Med Chem Lett. 2011 Sep 15;21(18):5171-6. Epub 2011 Jul 23. PMID:21831637[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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