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Crystal Structure of a flavoenzyme RutA in the pyrimidine catabolic pathway
Structural highlights
FunctionRUTA_ECOLI Catalyzes the pyrimidine ring opening between N-3 and C-4 by an unusual flavin hydroperoxide-catalyzed mechanism to yield ureidoacrylate peracid. It cleaves pyrmidine rings directly by adding oxygen atoms, making a toxic ureidoacrylate peracid product which can be spontaneously reduced to ureidoacrylate. Requires the flavin reductase RutF to regenerate FMN in vivo. RutF can be substituted by Fre in vitro.[1] [2] Publication Abstract from PubMedA new pyrimidine catabolic pathway (the Rut pathway) was recently discovered in Escherichia coli K12. In this pathway, uracil is converted to 3-hydroxypropionate, ammonia, and carbon dioxide. The seven-gene Rut operon is required for this conversion. Here we demonstrate that the flavoenzyme RutA catalyzes the initial uracil ring-opening reaction to give 3-ureidoacrylate. This reaction, while formally a hydrolysis reaction, proceeds by an oxidative mechanism initiated by the addition of a flavin hydroperoxide to the C4 carbonyl. While peroxide-catalyzed amide hydrolysis has chemical precedent, we are not aware of a prior example of analogous chemistry catalyzed by flavin hydroperoxides. This study further illustrates the extraordinary catalytic versatility of the flavin cofactor. Catalysis of a flavoenzyme-mediated amide hydrolysis.,Mukherjee T, Zhang Y, Abdelwahed S, Ealick SE, Begley TP J Am Chem Soc. 2010 Apr 28;132(16):5550-1. doi: 10.1021/ja9107676. PMID:20369853[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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