Structural highlights
Function
RUTA_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 PubMed
A 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 Also
References
- ↑ Loh KD, Gyaneshwar P, Markenscoff Papadimitriou E, Fong R, Kim KS, Parales R, Zhou Z, Inwood W, Kustu S. A previously undescribed pathway for pyrimidine catabolism. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5114-9. Epub 2006 Mar 15. PMID:16540542 doi:0600521103
- ↑ Kim KS, Pelton JG, Inwood WB, Andersen U, Kustu S, Wemmer DE. The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems. J Bacteriol. 2010 Aug;192(16):4089-102. doi: 10.1128/JB.00201-10. Epub 2010 Apr, 16. PMID:20400551 doi:http://dx.doi.org/10.1128/JB.00201-10
- ↑ Mukherjee T, Zhang Y, Abdelwahed S, Ealick SE, Begley TP. Catalysis of a flavoenzyme-mediated amide hydrolysis. J Am Chem Soc. 2010 Apr 28;132(16):5550-1. doi: 10.1021/ja9107676. PMID:20369853 doi:http://dx.doi.org/10.1021/ja9107676
