5k4t
From Proteopedia
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==Three-dimensional structure of L-threonine 3-dehydrogenase from Trypanosoma brucei refined to 2.1 angstroms== | ==Three-dimensional structure of L-threonine 3-dehydrogenase from Trypanosoma brucei refined to 2.1 angstroms== | ||
| - | <StructureSection load='5k4t' size='340' side='right' caption='[[5k4t]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='5k4t' size='340' side='right'caption='[[5k4t]], [[Resolution|resolution]] 2.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5k4t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K4T OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5k4t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K4T FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5k4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k4t OCA], [https://pdbe.org/5k4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k4t RCSB], [https://www.ebi.ac.uk/pdbsum/5k4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k4t ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q7YW97_9TRYP Q7YW97_9TRYP] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Two of the world's most neglected tropical diseases, human African trypanosomiasis (HAT) and Chagas disease, are caused by protozoan parasites of the genus Trypanosoma. These organisms possess specialized metabolic pathways, frequently distinct from those in humans, which have potential to be exploited as novel drug targets. This study elucidates the structure and function of L-threonine-3-dehydrogenase (TDH) from T. brucei, the causative pathogen of HAT. TDH is a key enzyme in the metabolism of L-threonine, and an inhibitor of TDH has been shown to have trypanocidal activity in the procyclic form of T. brucei. TDH is a nonfunctional pseudogene in humans, suggesting that it may be possible to rationally design safe and specific therapies for trypanosomiasis by targeting this parasite enzyme. As an initial step, the TDH gene from T. brucei was expressed and the three-dimensional structure of the enzyme was solved by X-ray crystallography. In multiple crystallographic structures, T. brucei TDH is revealed to be a dimeric short-chain dehydrogenase that displays a considerable degree of conformational variation in its ligand-binding regions. Geometric simulations of the structure have provided insight into the dynamic behaviour of this enzyme. Furthermore, structures of TDH bound to its natural substrates and known inhibitors have been determined, giving an indication of the mechanism of catalysis of the enzyme. Collectively, these results provide vital details for future drug design to target TDH or related enzymes. | ||
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| + | Structure and function of L-threonine-3-dehydrogenase from the parasitic protozoan Trypanosoma brucei revealed by X-ray crystallography and geometric simulations.,Adjogatse E, Erskine P, Wells SA, Kelly JM, Wilden JD, Chan AWE, Selwood D, Coker A, Wood S, Cooper JB Acta Crystallogr D Struct Biol. 2018 Sep 1;74(Pt 9):861-876. doi:, 10.1107/S2059798318009208. Epub 2018 Sep 3. PMID:30198897<ref>PMID:30198897</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5k4t" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Trypanosoma brucei]] |
| - | [[Category: | + | [[Category: Adjogatse EK]] |
| - | [[Category: | + | [[Category: Cooper JB]] |
| - | [[Category: | + | [[Category: Erskine PT]] |
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Current revision
Three-dimensional structure of L-threonine 3-dehydrogenase from Trypanosoma brucei refined to 2.1 angstroms
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