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Analogs of 1-phosphonooxy-2,2-dihydroxy-3-oxo-5-(methylthio)pentane, an acyclic intermediate in the methionine salvage pathway: a new preparation and characterization of activity with E1 enolase/phosphatase from Klebsiella oxytoca.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2004 Jul 15; Vol. 12 (14), pp. 3847-55. - Publication Year :
- 2004
-
Abstract
- The methionine salvage pathway allows the in vivo recovery of the methylthio moiety of methionine upon the formation of methylthioadenosine (MTA) from S-adenosylmethionine (SAM). The Fe(II)-containing form of acireductone dioxygenase (ARD) catalyzes the penultimate step in the pathway in Klebsiella oxytoca, the oxidative cleavage of the acireductone 1,2-dihydroxy-3-oxo-5-(methylthio)pent-1-ene (2) by dioxygen to give formate and 2-oxo-4-(methylthio)butyrate (3). The Ni(II)-bound form (Ni-ARD) catalyzes an off-pathway shunt, forming 3-(methylthio)propionate (4), carbon monoxide, and formate. Acireductone 2 is formed by the action of another enzyme, E1 enolase/phosphatase, on precursor 1-phosphonooxy-2,2-dihydroxy-3-oxo-5-methylthiopentane (1). Simple syntheses of several analogs of 1 are described, and their activity as substrates for E1 enolase/phosphatase characterized. A new bacterial overexpression system and purification procedure for E1, a member of the haloacid dehalogenase (HAD) superfamily, is described, and further characterization of the enzyme presented.
- Subjects :
- Amino Acid Sequence
Base Sequence
DNA Primers
Magnetic Resonance Spectroscopy
Methionine chemistry
Models, Molecular
Molecular Sequence Data
Phosphoric Monoester Hydrolases chemistry
Sequence Homology, Amino Acid
Spectrometry, Mass, Fast Atom Bombardment
Spectrophotometry, Ultraviolet
Klebsiella oxytoca enzymology
Methionine metabolism
Organophosphates chemistry
Pentanes chemistry
Phosphopyruvate Hydratase metabolism
Phosphoric Monoester Hydrolases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0968-0896
- Volume :
- 12
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15210152
- Full Text :
- https://doi.org/10.1016/j.bmc.2004.05.002