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| | ==Crystal structure of Drosophila melanogaster tryptophan 2,3-dioxygenase in complex with HEME== | | ==Crystal structure of Drosophila melanogaster tryptophan 2,3-dioxygenase in complex with HEME== |
| - | <StructureSection load='4hka' size='340' side='right' caption='[[4hka]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4hka' size='340' side='right'caption='[[4hka]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hka]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HKA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HKA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hka]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HKA 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></td></tr> | + | </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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">v, CG5163 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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=4hka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hka OCA], [https://pdbe.org/4hka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hka RCSB], [https://www.ebi.ac.uk/pdbsum/4hka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hka 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=4hka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hka OCA], [http://pdbe.org/4hka PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hka RCSB], [http://www.ebi.ac.uk/pdbsum/4hka PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hka ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/T23O_DROME T23O_DROME]] Catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring (By similarity). Required during larval growth to control the level of potentially harmful free tryptophan in the hemolymph. In the adult the same reaction is the first step in the ommochrome biosynthetic pathway.<ref>PMID:2108317</ref> | + | [https://www.uniprot.org/uniprot/T23O_DROME T23O_DROME] Catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring (By similarity). Required during larval growth to control the level of potentially harmful free tryptophan in the hemolymph. In the adult the same reaction is the first step in the ommochrome biosynthetic pathway.<ref>PMID:2108317</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Dioxygenase|Dioxygenase]] | + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Tryptophan 2,3-dioxygenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Ding, J]] | + | [[Category: Ding J]] |
| - | [[Category: Huang, W]] | + | [[Category: Huang W]] |
| - | [[Category: Catalytic mechanism]]
| + | |
| - | [[Category: Kynurenine pathway]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Regulatory mechanism]]
| + | |
| Structural highlights
Function
T23O_DROME Catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring (By similarity). Required during larval growth to control the level of potentially harmful free tryptophan in the hemolymph. In the adult the same reaction is the first step in the ommochrome biosynthetic pathway.[1]
Publication Abstract from PubMed
Tryptophan 2,3-dioxygenase (TDO) catalyzes the oxidative cleavage of the indole ring of l-tryptophan to N-formylkynurenine in the kynurenine pathway, and is considered as a drug target for cancer immunotherapy. Here, we report the first crystal structure of a eukaryotic TDO from Drosophila melanogaster (DmTDO) in complex with heme at 2.7A resolution. DmTDO consists of an N-terminal segment, a large domain and a small domain, and assumes a tetrameric architecture. Compared with prokaryotic TDOs, DmTDO contains two major insertion sequences: one forms part of the heme-binding site and the other forms a large portion of the small domain. The small domain which is unique to eukaryotic TDOs, interacts with the active site of an adjacent monomer and plays a role in the catalysis. Molecular modeling and dynamics simulation of DmTDO-heme-Trp suggest that like prokaryotic TDOs, DmTDO adopts an induced-fit mechanism to bind l-Trp; in particular, two conserved but flexible loops undergo conformational changes, converting the active site from an open conformation to a closed conformation. The functional roles of the key residues involved in recognition and binding of the heme and the substrate are verified by mutagenesis and kinetic studies. In addition, a modeling study of DmTDO in complex with the competitive inhibitor LM10 provides useful information for further inhibitor design. These findings reveal insights into the substrate recognition and the catalysis of DmTDO and possibly other eukaryotic TDOs and shed lights on the development of effective anti-TDO inhibitors.
Crystal structure of Drosophila melanogaster tryptophan 2,3-dioxygenase reveals insights into substrate recognition and catalytic mechanism.,Huang W, Gong Z, Li J, Ding J J Struct Biol. 2013 Mar;181(3):291-9. doi: 10.1016/j.jsb.2013.01.002. Epub 2013, Jan 17. PMID:23333332[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Searles LL, Ruth RS, Pret AM, Fridell RA, Ali AJ. Structure and transcription of the Drosophila melanogaster vermilion gene and several mutant alleles. Mol Cell Biol. 1990 Apr;10(4):1423-31. PMID:2108317
- ↑ Huang W, Gong Z, Li J, Ding J. Crystal structure of Drosophila melanogaster tryptophan 2,3-dioxygenase reveals insights into substrate recognition and catalytic mechanism. J Struct Biol. 2013 Mar;181(3):291-9. doi: 10.1016/j.jsb.2013.01.002. Epub 2013, Jan 17. PMID:23333332 doi:http://dx.doi.org/10.1016/j.jsb.2013.01.002
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