Abstract
Multifunctional enzyme, type‐1 (MFE1) is a monomeric enzyme with a 2E‐enoyl‐CoA hydratase and a 3S‐hydroxyacyl‐CoA dehydrogenase (HAD) active site. Enzyme kinetic data of rat peroxisomal MFE1 show that the catalytic efficiencies for converting the short‐chain substrate 2E‐butenoyl‐CoA into acetoacetyl‐CoA are much lower when compared with those of the homologous monofunctional enzymes. The mode of binding of acetoacetyl‐CoA (to the hydratase active site) and the very similar mode of binding of NAD + and NADH (to the HAD part) are described and compared with those of their monofunctional counterparts. Structural comparisons suggest that the conformational flexibility of the HAD and hydratase parts of MFE1 are correlated. The possible importance of the conformational flexibility of MFE1 for its biocatalytic properties is discussed.DatabaseStructural data are available in PDB database under the accession number 5MGB.
Highlights
Enzyme kinetic data of rat peroxisomal MFE1 show that the catalytic efficiencies for converting the short-chain substrate 2E-butenoylCoA into acetoacetyl-CoA are much lower when compared with those of the homologous monofunctional enzymes
In the AcAc-CoA/NAD+ complex structure, refined at 2.8 A resolution (Table 1), the AcAc-CoA is only bound in the hydratase active site
Concluding remarks In MFE1, the hydratase and dehydrogenase active sites are built by one polypeptide chain
Summary
Peroxisomal b-oxidation is catalyzed by monofunctional and multifunctional enzymes. The first step of the peroxisomal b-oxidation pathway (Fig. 1), the acyl-CoA oxidase reaction, and the fourth (last) step, the thiolase reaction, are catalyzed by monofunctional enzymes. The peroxisomal multifunctional enzyme, type-1 (MFE1) catalyzes the second and third steps. The third step of the b-oxidation pathway, the NAD-dependent dehydrogenation reaction of 3-hydroxyacyl-CoA (EC 1.1.1.35), is catalyzed by the C-terminal part of MFE1. Substrate specificity studies have shown that MFE1 can catalyze the hydration of long-chain linear acyl chains as well as of the bulky bile acid intermediates. The latter acyl moieties have a 2-methyl group
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