De novo protein design provides an attractive approach for the construction of models to probe the features required for the function of complex metalloproteins. These minimal models contain the essential elements believed necessary for activity of the protein. In this article, we summarize the design, structure determination, and functional properties of a family of artificial diiron proteins.
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http://dx.doi.org/10.1002/bip.20230 | DOI Listing |
ACS Chem Biol
August 2023
Institute of Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany.
Nonheme diiron monooxygenases (NHDMs) interact with nonribosomal peptide synthetase (NRPS) assembly lines to install β-hydroxylations at thiolation-domain-bound amino acids during nonribosomal peptide biosynthesis. The high potential of this enzyme family to diversify the products of engineered assembly lines is disproportionate to the currently small knowledge about their structures and mechanisms of substrate recognition. Here, we report the crystal structure of FrsH, the NHDM which catalyzes the β-hydroxylation of l-leucines during biosynthesis of the depsipeptide G protein inhibitor FR900359.
View Article and Find Full Text PDFJ Am Chem Soc
April 2023
Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, United States.
Despite significant efforts, it remains a challenge to design artificial enzymes that can mimic both structures and functions of natural enzymes. Here, we report the post-synthetic construction of binuclear iron catalysts in MOF-253 to mimic natural di-iron monooxygenases. The adjacent bipyridyl (bpy) linkers in MOF-253 can freely rotate to form the [(bpy)Fe(μ-OH)] active site in a self-adaptive fashion.
View Article and Find Full Text PDFNat Mater
August 2022
Department of Chemistry, University of Manchester, Manchester, UK.
Natural gas, consisting mainly of methane (CH), has a relatively low energy density at ambient conditions (~36 kJ l). Partial oxidation of CH to methanol (CHOH) lifts the energy density to ~17 MJ l and drives the production of numerous chemicals. In nature, this is achieved by methane monooxygenase with di-iron sites, which is extremely challenging to mimic in artificial systems due to the high dissociation energy of the C-H bond in CH (439 kJ mol) and facile over-oxidation of CHOH to CO and CO.
View Article and Find Full Text PDFChem Commun (Camb)
June 2022
Institute of Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan.
Carbon monoxide (CO) plays an important role in signaling in cells, making its use as a therapeutic tool highly intriguing. Reduced burst emissions are important to avoid the cytotoxicity and tissue damage caused by CO. Here, we developed a stable diiron carbonyl [FeFe] hydrogenase agent that enables prolonged CO release activity (half-life of over 9 h) in cells.
View Article and Find Full Text PDFJ Phys Chem B
January 2022
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Di-iron hydrogenases are a class of enzymes that are capable of reducing protons to form molecular hydrogen with high efficiency. In addition to the catalytic site, these enzymes have evolved dedicated pathways to transport protons and electrons to the reaction center. Here, we present a detailed study of the most likely proton transfer pathway in such an enzyme using QM/MM molecular dynamics simulations.
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