View source for 3mjy


==Crystal structure of dihydroorotate dehydrogenase from Leishmania major in complex with 5-Aminoorotic acid==
<StructureSection load='3mjy' size='340' side='right'caption='[[3mjy]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3mjy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MJY 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]] 1.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IJZ:5-AMINO-2,6-DIOXO-1,2,3,6-TETRAHYDROPYRIMIDINE-4-CARBOXYLIC+ACID'>IJZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3mjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mjy OCA], [https://pdbe.org/3mjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mjy RCSB], [https://www.ebi.ac.uk/pdbsum/3mjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mjy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q4QEW7_LEIMA Q4QEW7_LEIMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The enzyme dihydroorotate dehydrogenase (DHODH) has been suggested as a promising target for the design of trypanocidal agents. We report here the discovery of novel inhibitors of Trypanosoma cruzi DHODH identified by a combination of virtual screening and ITC methods. Monitoring of the enzymatic reaction in the presence of selected ligands together with structural information obtained from X-ray crystallography analysis have allowed the identification and validation of a novel site of interaction (S2 site). This has provided important structural insights for the rational design of T. cruzi and Leishmania major DHODH inhibitors. The most potent compound (1) in the investigated series inhibits TcDHODH enzyme with Kiapp value of 19.28 muM and possesses a ligand efficiency of 0.54 kcal mol(-1) per non-H atom. The compounds described in this work are promising hits for further development.

Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery.,Cheleski J, Rocha JR, Pinheiro MP, Wiggers HJ, da Silva AB, Nonato MC, Montanari CA Eur J Med Chem. 2010 Dec;45(12):5899-909. Epub 2010 Oct 7. PMID:20965617<ref>PMID:20965617</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3mjy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania major]]
[[Category: Cheleski J]]
[[Category: Montanari CA]]
[[Category: Nonato MC]]
[[Category: Pinheiro MP]]
[[Category: Rocha JR]]