{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(9)"],"submitter":["Brissos V"],"pubmed_abstract":["Laccases are in increasing demand as innovative solutions in the biorefinery fields. Here, we combine mutagenesis with structural, kinetic, and <i>in silico</i> analyses to characterize the molecular features that cause the evolution of a hyperthermostable metallo-oxidase from the multicopper oxidase family into a laccase (<i>k</i> <sub>cat</sub> 273 s<sup>-1</sup> for a bulky aromatic substrate). We show that six mutations scattered across the enzyme collectively modulate dynamics to improve the binding and catalysis of a bulky aromatic substrate. The replacement of residues during the early stages of evolution is a stepping stone for altering the shape and size of substrate-binding sites. Binding sites are then fine-tuned through high-order epistasis interactions by inserting distal muta"],"journal":["ACS catalysis"],"pagination":["5022-5035"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9775220"],"repository":["biostudies-literature"],"pubmed_title":["Distal Mutations Shape Substrate-Binding Sites during Evolution of a Metallo-Oxidase into a Laccase."],"pmcid":["PMC9775220"],"pubmed_authors":["Borges PT","Lucas MF","Masgrau L","Frazao C","Cordeiro TN","Martins LO","Monza E","Brissos V","Nunez-Franco R"],"additional_accession":[]},"is_claimable":false,"name":"Distal Mutations Shape Substrate-Binding Sites during Evolution of a Metallo-Oxidase into a Laccase.","description":"Laccases are in increasing demand as innovative solutions in the biorefinery fields. Here, we combine mutagenesis with structural, kinetic, and <i>in silico</i> analyses to characterize the molecular features that cause the evolution of a hyperthermostable metallo-oxidase from the multicopper oxidase family into a laccase (<i>k</i> <sub>cat</sub> 273 s<sup>-1</sup> for a bulky aromatic substrate). We show that six mutations scattered across the enzyme collectively modulate dynamics to improve the binding and catalysis of a bulky aromatic substrate. The replacement of residues during the early stages of evolution is a stepping stone for altering the shape and size of substrate-binding sites. Binding sites are then fine-tuned through high-order epistasis interactions by inserting distal muta","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-05T14:57:40.434Z","creation":"2025-04-05T14:57:40.434Z"},"accession":"S-EPMC9775220","cross_references":{"pubmed":["36567772"],"doi":["10.1021/acscatal.2c00336"]}}