7uf8

Structure of CtdP in complex with penicimutamide E and NADP+

spinqualitylabelsall models 7uf8, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7uf8 is a 4 chain structure with sequence from Penicillium citrinum. 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: EDO, MSE, N3L, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The Diels-Alder cycloaddition is one of the most powerful approaches in organic synthesis and is often used in the synthesis of important pharmaceuticals. Yet, strictly controlling the stereoselectivity of the Diels-Alder reactions is challenging, and great efforts are needed to construct complex molecules with desired chirality via organocatalysis or transition-metal strategies. Nature has evolved different types of enzymes to exquisitely control cyclization stereochemistry; however, most of the reported Diels-Alderases have been shown to only facilitate the energetically favourable diastereoselective cycloadditions. Here we report the discovery and characterization of CtdP, a member of a new class of bifunctional oxidoreductase/Diels-Alderase, which was previously annotated as an NmrA-like transcriptional regulator. We demonstrate that CtdP catalyses the inherently disfavoured cycloaddition to form the bicyclo[2.2.2]diazaoctane scaffold with a strict alpha-anti-selectivity. Guided by computational studies, we reveal a NADP(+)/NADPH-dependent redox mechanism for the CtdP-catalysed inverse electron demand Diels-Alder cycloaddition, which serves as the first example of a bifunctional Diels-Alderase that utilizes this mechanism. An NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity.,Liu Z, Rivera S, Newmister SA, Sanders JN, Nie Q, Liu S, Zhao F, Ferrara JD, Shih HW, Patil S, Xu W, Miller MD, Phillips GN, Houk KN, Sherman DH, Gao X Nat Chem. 2023 Apr;15(4):526-534. doi: 10.1038/s41557-022-01117-6. Epub 2023 Jan , 12. PMID:36635598 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA