View source for 8gil


==L-threonine 3-Dehydrogenase from Trypanosoma cruzi (apo form)==
<StructureSection load='8gil' size='340' side='right'caption='[[8gil]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gil]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GIL 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</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=8gil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gil OCA], [https://pdbe.org/8gil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gil RCSB], [https://www.ebi.ac.uk/pdbsum/8gil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gil ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q4CU39_TRYCC Q4CU39_TRYCC] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanosoma cruzi is a flagellated protozoan and the etiological agent of Chagas disease, a neglected tropical disease described by Carlos Chagas in 1909 that remains without appropriate diagnostics and treatment. Throughout its life cycle, T. cruzi undergoes through many different environments, requiring adaptation of its metabolism to different nutrition sources. Recent studies have confirmed the adaptability of T. cruzi metabolism to different carbon sources and encouraged a deeper investigation of related metabolic pathways. In the present study, we investigated the catabolism of threonine in T. cruzi epimastigotes cultivated in LIT medium and following 24h of starvation in PBS. In LIT medium, threonine, serine, and histidine were rapidly consumed concomitantly with carbohydrates during parasite exponential growth. When threonine was provided as the only carbon source to starved parasites, they excreted acetate and glycine, corroborating the activity of a mitochondrial threonine degradation pathway. Subsequently, we used a recombinant T. cruzi L-threonine dehydrogrenase (TcTDH) to screen the Chagas Box, an open-source collection of phenotypic hits, and identified compound TCMDC-143160 as a low micromolar TcTDH inhibitor (IC50 = 3.5 muM). When TCMDC-143160 was administrated to starved parasites, it inhibited the threonine degradation pathway. Finally, we report the crystal structure of TcTDH and characterize its allosteric activation by potassium. Collectively, these data demonstrate the relevance of threonine catabolism in T. cruzi metabolism and provide a set of tools to further investigate TcTDH as a potential drug target for Chagas disease.

Inhibition of L-threonine dehydrogenase from Trypanosoma cruzi reduces glycine and acetate production and interferes with parasite growth and viability.,Faria JDN, Eufrasio AG, Fagundes M, Lobo-Rojas A, Marchese L, de Lima Silva CC, Bezerra EHS, Mercaldi GF, Alborghetti MR, Sforca ML, Cordeiro AT J Biol Chem. 2025 Feb;301(2):108080. doi: 10.1016/j.jbc.2024.108080. Epub 2024 , Dec 13. PMID:39675710<ref>PMID:39675710</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8gil" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma cruzi]]
[[Category: Bezerra EHS]]
[[Category: Cordeiro AT]]
[[Category: Fagundes M]]
[[Category: Faria JN]]
[[Category: Mercaldi GF]]