3srs: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines== | ==S. aureus Dihydrofolate Reductase complexed with novel 7-aryl-2,4-diaminoquinazolines== | ||
<StructureSection load='3srs' size='340' side='right' caption='[[3srs]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='3srs' size='340' side='right'caption='[[3srs]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3srs]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3srs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SRS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M23:7-(5-BROMO-2-ETHOXYPHENYL)-6-METHYLQUINAZOLINE-2,4-DIAMINE'>M23</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M23:7-(5-BROMO-2-ETHOXYPHENYL)-6-METHYLQUINAZOLINE-2,4-DIAMINE'>M23</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]], [[3sru|3sru]], [[3srw|3srw]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sqy|3sqy]], [[3sr5|3sr5]], [[3srq|3srq]], [[3srr|3srr]], [[3sru|3sru]], [[3srw|3srw]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">folA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3srs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3srs OCA], [https://pdbe.org/3srs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3srs RCSB], [https://www.ebi.ac.uk/pdbsum/3srs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3srs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 23: | ||
==See Also== | ==See Also== | ||
*[[Dihydrofolate reductase|Dihydrofolate reductase]] | *[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 29: | Line 29: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
[[Category: Large Structures]] | |||
[[Category: Hilgers, M]] | [[Category: Hilgers, M]] | ||
[[Category: Dhfr]] | [[Category: Dhfr]] | ||
Revision as of 11:07, 29 June 2022
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
Function[DYR_STAAU] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. 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
|
| ||||||||||||||||||||||