Comparison between medium-chain acyl-CoA dehydrogenase mutant proteins overexpressed in bacterial and mammalian cells

Abstract
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially lethal inherited defect in the β-oxidation of fatty acids. By comparing the behaviour of five missense MCAD mutant proteins expressed in COS cells and in Escherichia coli, we can define some of these as “pure folding mutants.” Upon expression in E. coli, these mutant proteins produce activity levels in the range of the wild-typeenzyme only if the chaperonins GroESL are co-overproduced. When Over expressed in COS cells, the pure folding mutants display enzyme activities comparable to the wild-type enzyme. The results suggest that the MCAD mutations can be modulated by chaperones, a phenomenon that may influence the manifestation of the MCAD disease.

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