This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


4lae

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:18, 1 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines==
==Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines==
-
<StructureSection load='4lae' size='340' side='right' caption='[[4lae]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
+
<StructureSection load='4lae' size='340' side='right'caption='[[4lae]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4lae]] is a 1 chain structure with sequence from [http://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=4LAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LAE FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4lae]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LAE FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1VM:7-[5,6-DIMETHYL-2-(1,3-THIAZOL-2-YL)-1H-BENZIMIDAZOL-1-YL]QUINAZOLINE-2,4-DIAMINE'>1VM</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lag|4lag]], [[4lah|4lah]], [[4lek|4lek]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1VM:7-[5,6-DIMETHYL-2-(1,3-THIAZOL-2-YL)-1H-BENZIMIDAZOL-1-YL]QUINAZOLINE-2,4-DIAMINE'>1VM</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4lae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lae OCA], [https://pdbe.org/4lae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lae RCSB], [https://www.ebi.ac.uk/pdbsum/4lae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lae ProSAT]</span></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=4lae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lae OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lae RCSB], [http://www.ebi.ac.uk/pdbsum/4lae PDBsum]</span></td></tr>
+
</table>
</table>
== Function ==
== 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.
+
[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;">
+
-
== Publication Abstract from PubMed ==
+
-
A new series of dihydrofolate reductase (DHFR) inhibitors, the 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines, were designed and optimized for antibacterial potency and enzyme selectivity. The most potent inhibitors in this series contained a five-membered heterocycle at the 2-position of the benzimidazole, leading to highly potent and selective compounds that exploit the differences in the size of a binding pocket adjacent to the NADPH cofactor between the bacterial and human DHFR enzymes. Typical of these compounds is 7-((2-thiazol-2-yl)benzimidazol-1-yl)-2,4 diaminoquinazoline, which is a potent inhibitor of S. aureus DHFR (Ki = 0.002 nM) with 46700-fold selectivity over human DHFR. This compound also has high antibacterial potency on Gram-positive bacteria with an MIC versus wild type S. aureus of 0.0125 mug/mL and a MIC versus trimethoprim-resistant S. aureus of 0.25 mug/mL. In vivo efficacy versus a S. aureus septicemia was demonstrated, highlighting the potential of this new series.
+
-
 
+
-
Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines.,Lam T, Hilgers MT, Cunningham ML, Kwan BP, Nelson KJ, Brown-Driver V, Ong V, Trzoss M, Hough G, Shaw KJ, Finn J J Med Chem. 2014 Feb 13;57(3):651-68. doi: 10.1021/jm401204g. Epub 2014 Jan 16. PMID:24428639<ref>PMID:24428639</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
==See Also==
==See Also==
-
*[[Dihydrofolate reductase|Dihydrofolate reductase]]
+
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Dihydrofolate reductase]]
+
[[Category: Large Structures]]
-
[[Category: Hilgers, M T]]
+
[[Category: Staphylococcus aureus]]
-
[[Category: Dhfr]]
+
[[Category: Hilgers MT]]
-
[[Category: Folate]]
+
-
[[Category: Nadph]]
+
-
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
+
-
[[Category: Protein-inhibitor complex]]
+

Current revision

Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines

PDB ID 4lae

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lae"
Personal tools