7ZN6

Crystal structure of laccase-like multicopper oxidase (LMCO) from Thermothelomyces thermophilus

Summary for 7ZN6

• Entry DOI: 10.2210/pdb7zn6/pdb
• Descriptor: Laccase-like multicopper oxidase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Thermothelomyces thermophilus ATCC 42464
• Total number of polymer chains: 1
• Total formula weight: 74239.10

Authors

Kosinas, C.,Dimarogona, M.,Zerva, A.,Topakas, E. (deposition date: 2022-04-20, release date: 2023-06-28, Last modification date: 2024-10-23)

Primary citation

Kosinas, C.,Zerva, A.,Topakas, E.,Dimarogona, M.
Structure-function studies of a novel laccase-like multicopper oxidase from Thermothelomyces thermophila provide insights into its biological role.
Acta Crystallogr D Struct Biol, 79:641-654, 2023

PubMed Abstract: Multicopper oxidases are promiscuous biocatalysts with great potential for the production of industrial compounds. This study is focused on the elucidation of the structure-function determinants of a novel laccase-like multicopper oxidase from the thermophilic fungus Thermothelomyces thermophila (TtLMCO1), which is capable of oxidizing both ascorbic acid and phenolic compounds and thus is functionally categorized between the ascorbate oxidases and fungal ascomycete laccases (asco-laccases). The crystal structure of TtLMCO1, determined using an AlphaFold2 model due to a lack of experimentally determined structures of close homologues, revealed a three-domain laccase with two copper sites, lacking the C-terminal plug observed in other asco-laccases. Analysis of solvent tunnels highlighted the amino acids that are crucial for proton transfer into the trinuclear copper site. Docking simulations showed that the ability of TtLMCO1 to oxidize ortho-substituted phenols stems from the movement of two polar amino acids at the hydrophilic side of the substrate-binding region, providing structural evidence for the promiscuity of this enzyme.

PubMed: 37326583
DOI: 10.1107/S2059798323004175

Experimental method

X-RAY DIFFRACTION (1.9 Å)