7YAV
Crystal structure of Diels-Alderase MaDA1
Summary for 7YAV
| Entry DOI | 10.2210/pdb7yav/pdb |
| Descriptor | MaDA1, FLAVIN-ADENINE DINUCLEOTIDE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | natural product biosynthetic enzyme, plant protein |
| Biological source | Morus alba |
| Total number of polymer chains | 2 |
| Total formula weight | 124544.95 |
| Authors | |
| Primary citation | Ding, Q.,Guo, N.,Gao, L.,McKee, M.,Wu, D.,Yang, J.,Fan, J.,Weng, J.K.,Lei, X. The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba. Nat Commun, 15:2492-2492, 2024 Cited by PubMed Abstract: Biosynthetic enzymes evolutionarily gain novel functions, thereby expanding the structural diversity of natural products to the benefit of host organisms. Diels-Alderases (DAs), functionally unique enzymes catalysing [4 + 2] cycloaddition reactions, have received considerable research interest. However, their evolutionary mechanisms remain obscure. Here, we investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites. Our findings suggest that these DAs have evolved from an ancestor functioning as a flavin adenine dinucleotide (FAD)-dependent oxidocyclase (OC), which catalyses the oxidative cyclisation reactions of isoprenoid-substituted phenolic compounds. Through crystal structure determination, computational calculations, and site-directed mutagenesis experiments, we identified several critical substitutions, including S348L, A357L, D389E and H418R that alter the substrate-binding mode and enable the OCs to gain intermolecular DA activity during evolution. This work provides mechanistic insights into the evolutionary rationale of DAs and paves the way for mining and engineering new DAs from other protein families. PubMed: 38509059DOI: 10.1038/s41467-024-46845-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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