5dlv | pdb_00005dlv

Crystal structure of Autotaxin (ENPP2) with tauroursodeoxycholic acid (TUDCA)

spinqualitylabelsall models 5dlv, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dlv is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: 5D5, BMA, CA, GOL, IOD, MAN, NA, NAG, PO4, SCN, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENPP2_RAT Publication Abstract from PubMed Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7alpha-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs. Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.,Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A Nat Commun. 2016 Apr 14;7:11248. doi: 10.1038/ncomms11248. PMID:27075612 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures

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