title: Identification of activators of methionine sulfoxide reductases A and B.
abstract: The methionine sulfoxide reductase (Msr) family of enzymes has been shown to protect cells against oxidative damage. The two major Msr enzymes, MsrA and MsrB, can repair oxidative damage to proteins due to reactive oxygen species, by reducing the methionine sulfoxide in proteins back to methionine. A role of MsrA in animal aging was first demonstrated in Drosophila melanogaster where transgenic flies over-expressing recombinant bovine MsrA had a markedly extended life span. Subsequently, MsrA was also shown to be involved in the life span extension in Caenorhabditis elegans. These results supported other studies that indicated up-regulation, or activation, of the normal cellular protective mechanisms that cells use to defend against oxidative damage could be an approach to treat age related diseases and slow the aging process. In this study we have identified, for the first time, compounds structurally related to the natural products fusaricidins that markedly activate recombinant bovine and human MsrA and human MsrB.
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida, USA.
authors.forename: Predrag
authors.initials: P
authors.lastname: Cudic
authors.affiliation: Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, FL, USA.
authors.forename: Neelambari
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, FL, USA.
authors.forename: Daphna
authors.initials: D
authors.lastname: Sagher
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida, USA.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Williams
authors.affiliation: Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, FL, USA; Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: Maciej J
authors.initials: MJ
authors.lastname: Stawikowski
authors.affiliation: Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, FL, USA. Electronic address: hweissba@fau.edu.
authors.forename: Herbert
authors.initials: H
authors.lastname: Weissbach
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry*; D055808:Drug Discovery / Q000379:methods*; D004789:Enzyme Activation; D004795:Enzyme Stability; D051150:Methionine Sulfoxide Reductases / Q000037:antagonists & inhibitors*; D008840:Microfilament Proteins; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D001426:Bacterial Proteins; D047630:Depsipeptides; D008840:Microfilament Proteins; D014157:Transcription Factors; C099200:fusaricidin A; C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase
keywords: Fusaricidin analogues; Methionine sulfoxide reductases; Msr activation