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Crystal structure of laccase-like multicopper oxidase (LMCO) from Thermothelomyces thermophilus
Structural highlights
FunctionLMCO1_THET4 Yellow laccase-like multicopper oxidase that is able to oxidize a variety of phenolic compounds including standard laccase substrates such as 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,6-dimethoxyphenol (2,6-DMP) (PubMed:30529567, PubMed:37326583). The existence of an ortho-hydroxy group is crucial for oxidation since pyrogallol and catechol, which contain ortho-hydroxy groups, are readily oxidized, which is not the case for resorcinol and hydroquinone, that contain meta- and para-hydroxy groups, respectively (PubMed:37326583). The same is also true for the existence of a methoxy group in an ortho-position, since 2,6-DMP, guaiacol and ferulic and caffeic acids are also rather easily oxidized compared with the corresponding unsubstituted compound (PubMed:37326583). Can be used for the bioconversion of 2',3,4-trihy-droxychalcone to 3',4'-dihydroxy-aurone, a bioactive aurone recently shown to possess inhibitory activity against several isoforms of the histone deacetylase complex (HDAC) (PubMed:30529567).[1] [2] Publication Abstract from PubMedMulticopper 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. Structure-function studies of a novel laccase-like multicopper oxidase from Thermothelomyces thermophila provide insights into its biological role.,Kosinas C, Zerva A, Topakas E, Dimarogona M Acta Crystallogr D Struct Biol. 2023 Jul 1;79(Pt 7):641-654. doi: , 10.1107/S2059798323004175. Epub 2023 Jun 16. PMID:37326583[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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