A mixed-valent Fe(II)Fe(III) species converts cysteine to an oxazolone/thioamide pair in methanobactin biosynthesis.

Autor:	Park YJ; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Jodts RJ; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Slater JW; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802.; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802., Reyes RM; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Winton VJ; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Montaser RA; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Thomas PM; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Dowdle WB; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Ruiz A; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Kelleher NL; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Bollinger JM Jr; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802.; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802., Krebs C; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802.; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802., Hoffman BM; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208., Rosenzweig AC; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.; Department of Chemistry, Northwestern University, Evanston, IL 60208.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Mar 29; Vol. 119 (13), pp. e2123566119. Date of Electronic Publication: 2022 Mar 23.
DOI:	10.1073/pnas.2123566119
Abstrakt:	SignificanceMethanobactins (Mbns), copper-binding peptidic compounds produced by some bacteria, are candidate therapeutics for human diseases of copper overload. The paired oxazolone-thioamide bidentate ligands of methanobactins are generated from cysteine residues in a precursor peptide, MbnA, by the MbnBC enzyme complex. MbnBC activity depends on the presence of iron and oxygen, but the catalytically active form has not been identified. Here, we provide evidence that a dinuclear Fe(II)Fe(III) center in MbnB, which is the only representative of a >13,000-member protein family to be characterized, is responsible for this reaction. These findings expand the known roles of diiron enzymes in biology and set the stage for mechanistic understanding, and ultimately engineering, of the MbnBC biosynthetic complex.
Databáze:	MEDLINE
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