Structure–activity studies with the αβ-dihydroxyacid dehydratase of Salmonella typhimurium
| Autor: | Frank B. Armstrong, P. Morgan, Elizabeth L. Lipscomb, David H. G. Crout |
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| Rok vydání: | 1985 |
| Předmět: | |
| Zdroj: | J. Chem. Soc., Perkin Trans. 1. :691-696 |
| ISSN: | 1364-5463 0300-922X |
| DOI: | 10.1039/p19850000691 |
| Popis: | (2RS,3RS)- and (2RS,3SR)-2,3-Dihydroxybutanoic acids, (2R,3R)-2,3-dihydroxy-3-methypentanoic acid, (2RS)-2-ethyl-2,3-dihydroxypentanoic acid, (2RS,3RS)- and (2RS,3SR)-2,3-dihydroxy-3-methylhexanoic acids, and (2RS,3RS)- and (2RS,3SR)-2,3-dihydroxy-3-methylheptanoic acids were synthesised. These acids, as well as (RS)-2,3-dihydroxy-3-methylbutanoic acid and (RS)-glyceric acid were tested as substrates for the αβ-dihydroxyacid dehydratase of the isoteucine–valine biosynthetic pathway of Salmonella typhimurium. For acids having a propyl group at C-3, the activities were greatly reduced compared with those obtained for the natural substrates (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid [(2R,3R)-DHI] and (R)-2,3-dihydroxy-3-methylbutanoic acid [(R)-DHV]. For acids having an n-butyl substituent at C-3, the activities were close to zero. (2RS,3SR)-2,3-Dihydroxybutanoic acid (threo-isomer) underwent dehydration at a rate comparable with that of (2R,3R)-DHI, the natural substrate in the isoteucine pathway, whereas the (2RS,3RS)-acid (erythro-isomer) had much lower activity and (RS)-glyceric acid had even less activity. These results illustrate differences in the alkyl group requirements with respect to the areas of the binding site of the enzyme that accommodate the C-3 substituents. They also demonstrate the size limits of the alkyl groups that can be accommodated in substrate. analogues. |
| Databáze: | OpenAIRE |
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