3roa: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Candida glabrata dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(morpholin-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1004)== | ==Candida glabrata dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(morpholin-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1004)== | ||
<StructureSection load='3roa' size='340' side='right' caption='[[3roa]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='3roa' size='340' side='right'caption='[[3roa]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3roa]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3roa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_2001 Atcc 2001]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ROA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ROA FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=06V:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(MORPHOLIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06V</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=06V:6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(MORPHOLIN-4-YL)PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE'>06V</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ro9|3ro9]], [[3qlx|3qlx]], [[3qly|3qly]], [[3qlz|3qlz]], [[3eej|3eej]], [[3eek|3eek]], [[3eel|3eel]], [[3eem|3eem]], [[3cse|3cse]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ro9|3ro9]], [[3qlx|3qlx]], [[3qly|3qly]], [[3qlz|3qlz]], [[3eej|3eej]], [[3eek|3eek]], [[3eel|3eel]], [[3eem|3eem]], [[3cse|3cse]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAGL0J03894g, DHFR ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAGL0J03894g, DHFR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5478 ATCC 2001])</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=3roa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3roa OCA], [https://pdbe.org/3roa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3roa RCSB], [https://www.ebi.ac.uk/pdbsum/3roa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3roa ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 23: | Line 23: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Atcc 2001]] | [[Category: Atcc 2001]] | ||
[[Category: Large Structures]] | |||
[[Category: Anderson, A C]] | [[Category: Anderson, A C]] | ||
[[Category: Paulsen, J L]] | [[Category: Paulsen, J L]] | ||
Revision as of 13:19, 22 June 2022
Candida glabrata dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(morpholin-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1004)Candida glabrata dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(morpholin-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1004)
Structural highlights
Publication Abstract from PubMedA novel strategy for targeting the pathogenic organisms Candida albicans and Candida glabrata focuses on the development of potent and selective antifolates effective against dihydrofolate reductase. Crystal structure analysis suggested that an essential loop at the active site (Thr 58-Phe 66) differs from the analogous residues in the human enzyme, potentially providing a mechanism for achieving selectivity. In order to probe the role of this loop, we employed chemical synthesis, crystal structure determination and molecular dynamics simulations. The results of these analyses show that the loop residues undergo ligand-induced conformational changes that are similar among the fungal and human species. Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species.,Paulsen JL, Viswanathan K, Wright DL, Anderson AC Bioorg Med Chem Lett. 2013 Mar 1;23(5):1279-84. doi: 10.1016/j.bmcl.2013.01.008. , Epub 2013 Jan 11. PMID:23375226[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||