5eud

S1P Lyase Bacterial Surrogate bound to N-(1-(4-(3-hydroxyprop-1-yn-1-yl)phenyl)-2-((4-methoxy-2,5-dimethylbenzyl)amino)ethyl)-5-methylisoxazole-3-carboxamide

spinqualitylabelsall models 5eud, resolution 2.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5eud is a 2 chain structure with sequence from Symbiobacterium thermophilum IAM 14863. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.24Å Ligands: 5S6, LLP, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q67PY4_SYMTH Publication Abstract from PubMed S1P Lyase (SPL) has been described as a drug target in the treatment of autoimmune diseases. It plays an important role in maintaining intracellular levels of S1P thereby affecting T cell egress from lymphoid tissues. Several groups have already published approaches to inhibit S1P Lyase with small molecules, which in turn increase endogenous S1P concentrations resulting in immunosuppression. The use of structural biology has previously aided SPL inhibitor design. Novel construct design is at times necessary to provide a reagent for protein crystallography. Here we present a chimeric bacterial protein scaffold used for protein X-ray structures in the presence of early small molecule inhibitors. Mutations were introduced to the bacterial SPL from Symbiobacterium thermophilum which mimic the human enzyme. As a result, two mutant StSPL crystal structures resolved to 2.8A and 2.2A resolutions were solved and provide initial structural hypotheses for an isoxazole chemical series, whose optimization is discussed in the accompanying paper. Creation of a S1P Lyase bacterial surrogate for structure-based drug design.,Argiriadi MA, Banach D, Radziejewska E, Marchie S, DiMauro J, Dinges J, Dominguez E, Hutchins C, Judge RA, Queeney K, Wallace G, Harris CM Bioorg Med Chem Lett. 2016 May 1;26(9):2293-6. doi: 10.1016/j.bmcl.2016.02.084., Epub 2016 Mar 3. PMID:27013389 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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