View source for 4cjx


==The crystal structure of Trypanosoma brucei N5, N10- methylenetetrahydrofolate dehydrogenase-cyclohydrolase (FolD) complexed with NADP cofactor and inhibitor==
<StructureSection load='4cjx' size='340' side='right'caption='[[4cjx]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cjx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CJX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CJX 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9L9:(2S)-2-[[4-[[2,4-BIS(AZANYL)-6-OXIDANYLIDENE-1H-PYRIMIDIN-5-YL]CARBAMOYLAMINO]PHENYL]CARBONYLAMINO]PENTANEDIOIC+ACID'>9L9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=4cjx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cjx OCA], [https://pdbe.org/4cjx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cjx RCSB], [https://www.ebi.ac.uk/pdbsum/4cjx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cjx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q57WP0_TRYB2 Q57WP0_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The bifunctional enzyme N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (FolD) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 muM, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 muM). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP(+) and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors.

Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido Based Inhibitors of Trypanosoma brucei FolD and Testing for Antiparasitic Activity.,Eadsforth TC, Pinto A, Luciani R, Tamborini L, Cullia G, De Micheli C, Marinelli L, Cosconati S, Novellino E, Lo Presti L, Cordeiro da Silva A, Conti P, Hunter WN, Costi MP J Med Chem. 2015 Oct 22;58(20):7938-48. doi: 10.1021/acs.jmedchem.5b00687. Epub, 2015 Sep 16. PMID:26322631<ref>PMID:26322631</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cjx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei TREU927]]
[[Category: Eadsforth TC]]
[[Category: Hunter WN]]