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| | <StructureSection load='5ti9' size='340' side='right'caption='[[5ti9]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='5ti9' size='340' side='right'caption='[[5ti9]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ti9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TI9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TI9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ti9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TI9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NFK:N-FORMYLKYNURENINE'>NFK</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</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]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tia|5tia]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NFK:N-FORMYLKYNURENINE'>NFK</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TDO2, TDO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ti9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ti9 OCA], [https://pdbe.org/5ti9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ti9 RCSB], [https://www.ebi.ac.uk/pdbsum/5ti9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ti9 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptophan_2,3-dioxygenase Tryptophan 2,3-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.11 1.13.11.11] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ti9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ti9 OCA], [http://pdbe.org/5ti9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ti9 RCSB], [http://www.ebi.ac.uk/pdbsum/5ti9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ti9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/T23O_HUMAN T23O_HUMAN]] Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity). | + | [https://www.uniprot.org/uniprot/T23O_HUMAN T23O_HUMAN] Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity). |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Tryptophan 2,3-dioxygenase]]
| + | [[Category: Forouhar F]] |
| - | [[Category: Forouhar, F]] | + | [[Category: Karkashon S]] |
| - | [[Category: Karkashon, S]] | + | [[Category: Lew S]] |
| - | [[Category: Lew, S]] | + | [[Category: Lewis-Ballester A]] |
| - | [[Category: Lewis-Ballester, A]] | + | [[Category: Seetharaman J]] |
| - | [[Category: Seetharaman, J]] | + | [[Category: Tong L]] |
| - | [[Category: Tong, L]] | + | [[Category: Yeh SR]] |
| - | [[Category: Yeh, S R]] | + | |
| - | [[Category: 3-dioxygenase in complex with trp and o2]]
| + | |
| - | [[Category: Human tryptophan 2]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
5ti9 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
T23O_HUMAN Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity).
Publication Abstract from PubMed
Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) play a central role in tryptophan metabolism and are involved in many cellular and disease processes. Here we report the crystal structure of human TDO (hTDO) in a ternary complex with the substrates L-Trp and O2 and in a binary complex with the product N-formylkynurenine (NFK), defining for the first time the binding modes of both substrates and the product of this enzyme. The structure indicates that the dioxygenation reaction is initiated by a direct attack of O2 on the C2 atom of the L-Trp indole ring. The structure also reveals an exo binding site for L-Trp, located ~42 A from the active site and formed by residues conserved among tryptophan-auxotrophic TDOs. Biochemical and cellular studies indicate that Trp binding at this exo site does not affect enzyme catalysis but instead it retards the degradation of hTDO through the ubiquitin-dependent proteasomal pathway. This exo site may therefore provide a novel L-Trp-mediated regulation mechanism for cellular degradation of hTDO, which may have important implications in human diseases.
Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase.,Lewis-Ballester A, Forouhar F, Kim SM, Lew S, Wang Y, Karkashon S, Seetharaman J, Batabyal D, Chiang BY, Hussain M, Correia MA, Yeh SR, Tong L Sci Rep. 2016 Oct 20;6:35169. doi: 10.1038/srep35169. PMID:27762317[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lewis-Ballester A, Forouhar F, Kim SM, Lew S, Wang Y, Karkashon S, Seetharaman J, Batabyal D, Chiang BY, Hussain M, Correia MA, Yeh SR, Tong L. Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. Sci Rep. 2016 Oct 20;6:35169. doi: 10.1038/srep35169. PMID:27762317 doi:http://dx.doi.org/10.1038/srep35169
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