biostudies-literatureSelvan DUniversity of MississippiCollege of Liberal Arts, University of Mississippi10317https://www.ebi.ac.uk/biostudies/studies/S-EPMC10299331biostudies-literatureUnknown24(12)We present a Ni_p site model of acetyl coenzyme-A synthase (ACS) within a de novo-designed trimer peptide that self-assembles to produce a homoleptic Ni(Cys)₃ binding motif. Spectroscopic and kinetic studies of ligand binding demonstrate that Ni binding stabilizes the peptide assembly and produces a terminal Ni^I-CO complex. When the CO-bound state is reacted with a methyl donor, a new species is quickly produced with new spectral features. While the metal-bound CO is albeit unactivated, the presence of the methyl donor produces an activated metal-CO complex. Selective outer sphere steric modifications demonstrate that the physical properties of the ligand-bound states are altered differently depending on the location of the steric modification above or below the Ni site.International journal of molecular sciencesA De Novo Designed Trimeric Metalloprotein as a Ni_p Model of the Acetyl-CoA Synthase.PMC10299331N/ASelvan DChakraborty SfalseA De Novo Designed Trimeric Metalloprotein as a Ni_p Model of the Acetyl-CoA Synthase.We present a Ni_p site model of acetyl coenzyme-A synthase (ACS) within a de novo-designed trimer peptide that self-assembles to produce a homoleptic Ni(Cys)₃ binding motif. Spectroscopic and kinetic studies of ligand binding demonstrate that Ni binding stabilizes the peptide assembly and produces a terminal Ni^I-CO complex. When the CO-bound state is reacted with a methyl donor, a new species is quickly produced with new spectral features. While the metal-bound CO is albeit unactivated, the presence of the methyl donor produces an activated metal-CO complex. Selective outer sphere steric modifications demonstrate that the physical properties of the ligand-bound states are altered differently depending on the location of the steric modification above or below the Ni site.2023-01-01T00:00:00Z2023 Jun2026-04-08T12:39:32.725Z2025-04-07T10:22:05.429ZS-EPMC102993313737346410.3390/ijms241210317