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| | <StructureSection load='5lc1' size='340' side='right'caption='[[5lc1]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='5lc1' size='340' side='right'caption='[[5lc1]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lc1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LC1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LC1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lc1]] is a 6 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=5LC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LC1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> | + | </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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-threonine_3-dehydrogenase L-threonine 3-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.103 1.1.1.103] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lc1 OCA], [http://pdbe.org/5lc1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lc1 RCSB], [http://www.ebi.ac.uk/pdbsum/5lc1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lc1 ProSAT]</span></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=5lc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lc1 OCA], [https://pdbe.org/5lc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lc1 RCSB], [https://www.ebi.ac.uk/pdbsum/5lc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lc1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q7YW97_9TRYP Q7YW97_9TRYP] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: L-threonine 3-dehydrogenase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Adjogatse, E]] | + | [[Category: Trypanosoma brucei]] |
| - | [[Category: Cooper, J B]] | + | [[Category: Adjogatse E]] |
| - | [[Category: Erskine, P T]] | + | [[Category: Cooper JB]] |
| - | [[Category: Wood, S P]] | + | [[Category: Erskine PT]] |
| - | [[Category: Dehydrogenase]] | + | [[Category: Wood SP]] |
| - | [[Category: Holo-enzyme]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| Structural highlights
5lc1 is a 6 chain structure with sequence from Trypanosoma brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.1Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q7YW97_9TRYP
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Adjogatse E, Erskine P, Wells SA, Kelly JM, Wilden JD, Chan AWE, Selwood D, Coker A, Wood S, Cooper JB. Structure and function of L-threonine-3-dehydrogenase from the parasitic protozoan Trypanosoma brucei revealed by X-ray crystallography and geometric simulations. Acta Crystallogr D Struct Biol. 2018 Sep 1;74(Pt 9):861-876. doi:, 10.1107/S2059798318009208. Epub 2018 Sep 3. PMID:30198897 doi:http://dx.doi.org/10.1107/S2059798318009208
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