8ZLT

Co-crystal structure of MaDS1 with diene

This is a non-PDB format compatible entry.

Summary for 8ZLT

• Entry DOI: 10.2210/pdb8zlt/pdb
• Descriptor: MaDS1, FLAVIN-ADENINE DINUCLEOTIDE, methyl 4-[(1~{E})-7-methyl-3-methylidene-octa-1,6-dienyl]-3,5-bis(oxidanyl)benzoate, ... (4 entities in total)
• Functional Keywords: bbe-like enzyme, oxidase, flavoprotein, plant protein
• Biological source: Morus alba
• Total number of polymer chains: 2
• Total formula weight: 120024.42

Authors

Guo, N.,Yang, J.,Fan, J.,Lei, X. (deposition date: 2024-05-21, release date: 2025-08-13, Last modification date: 2025-10-15)

Primary citation

Guo, N.,Gu, J.,Zhou, Q.,Liu, F.,Dong, H.,Ding, Q.,Wang, Q.,Wu, D.,Yang, J.,Fan, J.,Gao, L.,Houk, K.N.,Lei, X.
Aspartic acid residues in BBE-like enzymes from Morus alba promote a function shift from oxidative cyclization to dehydrogenation.
Proc.Natl.Acad.Sci.USA, 122:e2504346122-e2504346122, 2025

PubMed Abstract: Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism underlying the selectivity remains unknown. Here, we elucidated the catalytic mechanism of BBE-like oxidases from involved in the oxidative cyclization and dehydrogenation of moracin C. X-ray crystal structures of a functionally promiscuous flavin adenine dinucleotide (FAD)-bound oxidase, MaDS1, with and without an oxidative dehydrogenation product were determined at 2.03 Å and 2.21 Å resolution, respectively. Structure-guided mutagenesis and sequence analysis have identified a conserved aspartic acid that directs the reaction toward the oxidative dehydrogenation pathway. A combination of density functional theory (DFT) calculations and molecular dynamics (MD) simulations has revealed that aspartic acid acts as the catalytic base to deprotonate the carbon-cation intermediate to generate the dehydrogenated product, which otherwise undergoes a spontaneous 6π electrocyclization in the oxidative cyclization pathway to furnish the 2H-benzopyran product.

PubMed: 40828030
DOI: 10.1073/pnas.2504346122

Experimental method

X-RAY DIFFRACTION (2.03 Å)