7UF8
Structure of CtdP in complex with penicimutamide E and NADP+
Summary for 7UF8
| Entry DOI | 10.2210/pdb7uf8/pdb |
| Descriptor | CtdP, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, Penicimutamide E, ... (5 entities in total) |
| Functional Keywords | diels-alderase, oxidioreductase, nmra-like, oxidoreductase |
| Biological source | Penicillium citrinum |
| Total number of polymer chains | 4 |
| Total formula weight | 160160.02 |
| Authors | Rivera, S.,Liu, Z.,Newmister, S.A.,Gao, X.,Sherman, D.H. (deposition date: 2022-03-22, release date: 2023-02-22, Last modification date: 2024-10-30) |
| Primary citation | Liu, Z.,Rivera, S.,Newmister, S.A.,Sanders, J.N.,Nie, Q.,Liu, S.,Zhao, F.,Ferrara, J.D.,Shih, H.W.,Patil, S.,Xu, W.,Miller, M.D.,Phillips, G.N.,Houk, K.N.,Sherman, D.H.,Gao, X. An NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity. Nat.Chem., 15:526-534, 2023 Cited by PubMed Abstract: 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 α-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. PubMed: 36635598DOI: 10.1038/s41557-022-01117-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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