5ti9

Crystal structure of human TDO in complex with Trp and dioxygen, Northeast Structural Genomics Consortium Target HR6161

spinqualitylabelsall models 5ti9, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: HEM, NFK, OXY, PO4, TRP 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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