9PZ4

Crystal structure of 2-methoxyhydroquinone dioxygenase (MhdA) from Gelatoporia subvermispora

Summary for 9PZ4

• Entry DOI: 10.2210/pdb9pz4/pdb
• Descriptor: homogentisate 1,2-dioxygenase, FE (III) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: dioxygenase, vanillate, 2-methoxyhydroquinone, white-rot fungi, lignin, oxidoreductase
• Biological source: Gelatoporia subvermispora B (White-rot fungus)
• Total number of polymer chains: 6
• Total formula weight: 331978.49

Authors

Mathews, I.I.,Kuatsjah, E.,Schwartz, A.,Sarangi, R.,McGeehan, J.E.,Salvachua, D. (deposition date: 2025-08-08, release date: 2026-06-10)

Primary citation

Schwartz, A.,Kuatsjah, E.,Mathews, I.I.,Mitchell, H.D.,Purvine, S.O.,Eder, E.K.,Hoyt, D.W.,Markillie, L.M.,Burnet, M.C.,Woodworth, S.P.,Ingraham, M.A.,Ramirez, K.J.,Monteiro, L.M.O.,Sarangi, R.,McGeehan, J.E.,Salvachua, D.
Catabolism of lignin-related methoxylated compounds in white-rot fungi utilizes non-canonical oxidoreductases.
Cell Rep, 45:117428-117428, 2026

PubMed Abstract: White-rot fungi (WRF) are the most effective lignin-degrading organisms in nature. Lignin is a highly methoxylated plant biopolymer, yet the pathways WRF use to metabolize methoxylated aromatic monomeric compounds as carbon sources remain unidentified. Using systems biology, we elucidate the intracellular catabolism of vanillate-a monomethoxylated aromatic compound-by Gelatoporia subvermispora and Trametes versicolor. We identify and biochemically validate a four-enzyme pathway that converts vanillate into β-ketoadipate, which enters central carbon metabolism. Unlike bacteria, which demethylate vanillate before ring-cleavage by intradiol dioxygenases, WRF employ oxidative decarboxylation followed by extradiol dioxygenase-mediated cleavage. A previously uncharacterized hydrolase is also shown to catalyze the terminal step of this pathway. Biochemical and structural approaches reveal non-canonical enzymes, including a highly substrate-specific extradiol dioxygenase and a metal-free, promiscuous reductase that acts on both methoxylated and non-methoxylated intermediates. These findings highlight distinct fungal strategies for aromatic degradation, offering insights into lignin valorization and wood decay mechanisms.

PubMed: 42217187
DOI: 10.1016/j.celrep.2026.117428

Experimental method

X-RAY DIFFRACTION (2.25 Å)