biostudies-literatureUnknown6(7)Fujieda NAs an alternative to Darwinian evolution relying on catalytic promiscuity, a protein may acquire auxiliary function upon metal binding, thus providing it with a novel catalytic machinery. Here we show that addition of cupric ions to a 6-phosphogluconolactonase 6-PGLac bearing a putative metal binding site leads to the emergence of peroxidase activity (kcat 7.8 × 10-2 s-1, KM 1.1 × 10-5 M). Both X-ray crystallographic and EPR data of the copper-loaded enzyme Cu·6-PGLac reveal a bis-histidine coordination site, located within a shallow binding pocket capable of accommodating the o-dianisidine substrate.Chemical science4060-4065https://www.ebi.ac.uk/biostudies/studies/S-EPMC5707476biostudies-literatureEnzyme repurposing of a hydrolase as an emergent peroxidase upon metal binding.PMC5707476Schatti JOhkubo KFukuzumi SWard TRMaier TFujieda NStuttfeld EfalseEnzyme repurposing of a hydrolase as an emergent peroxidase upon metal binding.As an alternative to Darwinian evolution relying on catalytic promiscuity, a protein may acquire auxiliary function upon metal binding, thus providing it with a novel catalytic machinery. Here we show that addition of cupric ions to a 6-phosphogluconolactonase 6-PGLac bearing a putative metal binding site leads to the emergence of peroxidase activity (kcat 7.8 × 10-2 s-1, KM 1.1 × 10-5 M). Both X-ray crystallographic and EPR data of the copper-loaded enzyme Cu·6-PGLac reveal a bis-histidine coordination site, located within a shallow binding pocket capable of accommodating the o-dianisidine substrate.2015-01-01T00:00:00Z2015 Jul2021-02-19T18:55:53Z2019-03-27T03:03:21ZS-EPMC57074762921817210.1039/c5sc01065a