Journal:Acta Cryst D:S2059798323004175
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
| - | This study presents the crystal structure of a novel laccase-like multicopper oxidase from a thermophilic fungus (''Thermothelomyces thermophila''), named ''Tt''LMCO1. Multicopper oxidases are biocatalysts with various biotechnological applications, such as wastewater treatment, synthesis of novel bioactive compounds, lignin degradation as well as biosensors development. This study is focused on ''Tt''LMCO1, which is capable of oxidizing both ascorbic acid and phenolic compounds and is thus functionally categorized between ascorbate oxidases and fungal laccases. <scene name='96/965740/Overall/2'>The crystal structure of TtLMCO1</scene>, determined using an AlphaFold 2.0 model in 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. The refined crystal structure of TtLMCO1 contains 576 residues arranged in three cupredoxin-like domains. <scene name='96/965740/Domain_a/1'>Domain A</scene> includes residues 11 to 134, <scene name='96/965740/Domain_b/1'>domain B</scene> includes residues 135-372 and <scene name='96/965740/Domain_c/1'>domain C</scene> includes residues 373-602. <scene name='96/965740/Disulfide_bond/1'>A unique disulfide bond is formed between Cys28 and Cys236</scene>, stabilizing the relative orientation between domains A and B. Each domain (A,B,C) is colored differently, with cyan, dark red and green respectively. The disulfide bond between residues Cys28 and Cys236 is in stick representation. Copper ions and a dioxygen molecule located at the trinuclear cluster (TNC) site are shown as brown and red spheres respectively. Glycans are depicted as cyan sticks. | + | This study presents the crystal structure of a novel laccase-like multicopper oxidase from a thermophilic fungus (''Thermothelomyces thermophila''), named ''Tt''LMCO1. Multicopper oxidases are biocatalysts with various biotechnological applications, such as wastewater treatment, synthesis of novel bioactive compounds, lignin degradation as well as biosensors development. This study is focused on ''Tt''LMCO1, which is capable of oxidizing both ascorbic acid and phenolic compounds and is thus functionally categorized between ascorbate oxidases and fungal laccases. <scene name='96/965740/Overall/2'>The crystal structure of TtLMCO1</scene>, determined using an AlphaFold 2.0 model in 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. The refined crystal structure of TtLMCO1 contains 576 residues arranged in three cupredoxin-like domains. <scene name='96/965740/Domain_a/1'>Domain A</scene> includes residues 11 to 134, <scene name='96/965740/Domain_b/1'>domain B</scene> includes residues 135-372 and <scene name='96/965740/Domain_c/1'>domain C</scene> includes residues 373-602. <scene name='96/965740/Disulfide_bond/1'>A unique disulfide bond is formed between Cys28 and Cys236</scene>, stabilizing the relative orientation between domains A and B. Each domain (A,B,C) is colored differently, with cyan, dark red and green respectively. The disulfide bond between residues Cys28 and Cys236 is in stick representation. Copper ions and a dioxygen molecule located at <scene name='96/965740/Trinuclear_cluster/1'>the trinuclear cluster (TNC) site</scene> are shown as brown and red spheres respectively. Glycans are depicted as cyan sticks. |
Analysis of solvent tunnels highlighted the amino acids that are crucial for proton transfer into the trinuclear copper site. Docking simulations with substrates that are oxidized by ''Tt''LMCO1 provide evidence that substrate specificity of these metallo-proteins is not exclusively related to their redox potential but also on the architecture of the binding site and the side chain flexibility of specific amino acids. Also, our analysis points to a potential biological role of these biocatalysts, involving the production of pigments and other bioactive compounds in their natural hosts. | Analysis of solvent tunnels highlighted the amino acids that are crucial for proton transfer into the trinuclear copper site. Docking simulations with substrates that are oxidized by ''Tt''LMCO1 provide evidence that substrate specificity of these metallo-proteins is not exclusively related to their redox potential but also on the architecture of the binding site and the side chain flexibility of specific amino acids. Also, our analysis points to a potential biological role of these biocatalysts, involving the production of pigments and other bioactive compounds in their natural hosts. | ||
Revision as of 14:29, 17 May 2023
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