View source for 4h97


==Candida albicans dihydrofolate reductase complexed with NADPH and 5-{3-[3-methoxy-5-(4-methylphenyl)phenyl]but-1-yn-1-yl}-6-methylpyrimidine-2,4-diamine (UCP111D4M)==
<StructureSection load='4h97' size='340' side='right'caption='[[4h97]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4h97]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H97 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=53S:5-[(3R)-3-(5-METHOXY-4-METHYLBIPHENYL-3-YL)BUT-1-YN-1-YL]-6-METHYLPYRIMIDINE-2,4-DIAMINE'>53S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></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=4h97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h97 OCA], [https://pdbe.org/4h97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h97 RCSB], [https://www.ebi.ac.uk/pdbsum/4h97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h97 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DYR_CANAX DYR_CANAX] 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 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<ref>PMID:23375226</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4h97" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Candida albicans]]
[[Category: Large Structures]]
[[Category: Anderson AC]]
[[Category: Paulsen JL]]