View source for 3srq

==S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines==
<StructureSection load='3srq' size='340' side='right' caption='[[3srq]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3srq]] 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=3SRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SRQ 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=Q19:1-[3-(2,4-DIAMINO-6-METHYLQUINAZOLIN-7-YL)PHENYL]ETHANONE'>Q19</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sqy|3sqy]], [[3sr5|3sr5]], [[3srr|3srr]], [[3srs|3srs]], [[3sru|3sru]], [[3srw|3srw]]</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=3srq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3srq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3srq RCSB], [http://www.ebi.ac.uk/pdbsum/3srq PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/DYR_STAAU DYR_STAAU]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Dihydrofolate reductase|Dihydrofolate reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dihydrofolate reductase]]
[[Category: Staphylococcus aureus]]
[[Category: Hilgers, M]]
[[Category: Dhfr]]
[[Category: Drug design]]
[[Category: Enzyme inhibitor]]
[[Category: Folate]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]