6s5j

Strictosidine Synthase from Ophiorrhiza pumila in complex with (S)-1-Ethyl-2,3,4,9-tetrahydro-1H-beta-carboline

spinqualitylabelsall models 6s5j, resolution 2.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6s5j is a 1 chain structure with sequence from Ophiorrhiza pumila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.42Å Ligands: KW8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q94LW9_9GENT Publication Abstract from PubMed The Pictet-Spengler reaction is a valuable route to 1,2,3,4-tetrahydro-beta-carboline (THBC) and isoquinoline scaffolds found in many important pharmaceuticals. Strictosidine synthase (STR) catalyzes the Pictet-Spengler condensation of tryptamine and the aldehyde secologanin to give (S)-strictosidine as a key intermediate in indole alkaloid biosynthesis. STRs also accept short-chain aliphatic aldehydes to give enantioenriched alkaloid products with up to 99% ee STRs are thus valuable asymmetric organocatalysts for applications in organic synthesis. The STR catalysis of reactions of small aldehydes gives an unexpected switch in stereopreference, leading to formation of the (R)-products. Here we report a rationale for the formation of the (R)-configured products by the STR enzyme from Ophiorrhiza pumila (OpSTR) using a combination of X-ray crystallography, mutational, and molecular dynamics (MD) studies. We discovered that short-chain aldehydes bind in an inverted fashion compared to secologanin leading to the inverted stereopreference for the observed (R)-product in those cases. The study demonstrates that the same catalyst can have two different productive binding modes for one substrate but give different absolute configuration of the products by binding the aldehyde substrate differently. These results will guide future engineering of STRs and related enzymes for biocatalytic applications. Inverted Binding of Non-natural Substrates in Strictosidine Synthase Leads to a Switch of Stereochemical Outcome in Enzyme-Catalyzed Pictet-Spengler Reactions.,Eger E, Simon A, Sharma M, Yang S, Breukelaar WB, Grogan G, Houk KN, Kroutil W J Am Chem Soc. 2020 Jan 15;142(2):792-800. doi: 10.1021/jacs.9b08704. Epub 2020, Jan 7. PMID:31909617 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Strictosidine Synthase

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