Structural enzymology comparisons of multifunctional enzyme, type‐1 (MFE1): the flexibility of its dehydrogenase part. Issue 12 (6th November 2017)

• Record Type: Journal Article
• Authors: Kasaragod, Prasad; Midekessa, Getnet B.; Sridhar, Shruthi; Schmitz, Werner; Kiema, Tiila‐Riikka; Hiltunen, Jukka K.; Wierenga, Rik K.
• Is Part Of: FEBS open bio. Volume 7:Issue 12(2017)
• Page Start: 1830
• Page End: 1842
• Publication Date: 2017-11-06
• Subjects: CoA -- crotonase -- dehydrogenase -- NAD -- substrate channeling; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12337
• Languages: English
• ISSNs: 2211-5463

Abstract

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. Database: Structural data are available in PDB database under the accession number5MGB . Abstract : Multifunctional enzyme, type‐1 (MFE1) is a monomeric enzyme, with a 2E‐enoyl‐CoA hydratase (blue, green) and a 3S‐hydroxyacyl‐CoA dehydrogenase (HAD, orange, red, yellow) active site. The mode of binding of acetoacetyl‐CoA (hydratase part) and NAD + (HAD part), shown as ball‐and‐stick models, is described. Structural comparisons suggest that the conformational flexibility (arrows) of MFE1 is possibly important for its biocatalytic properties.