title: Dissecting the sterol C-4 demethylation process in higher plants. From structures and genes to catalytic mechanism.
abstract: Sterols become functional only after removal of the two methyl groups at C-4. This review focuses on the sterol C-4 demethylation process in higher plants. An intriguing aspect in the removal of the two C-4 methyl groups of sterol precursors in plants is that it does not occur consecutively as it does in yeast and animals, but is interrupted by several enzymatic steps. Each C-4 demethylation step involves the sequential participation of three individual enzymatic reactions including a sterol methyl oxidase (SMO), a 3β-hydroxysteroid-dehydrogenase/C4-decarboxylase (3βHSD/D) and a 3-ketosteroid reductase (SR). The distant location of the two C-4 demethylations in the sterol pathway requires distinct SMOs with respective substrate specificity. Combination of genetic and molecular enzymological approaches allowed a thorough identification and functional characterization of two distinct families of SMOs genes and two 3βHSD/D genes. For the latter, these studies provided the first molecularly and functionally characterized HSDs from a short chain dehydrogenase/reductase family in plants, and the first data on 3-D molecular interactions of an enzyme of the postoxidosqualene cyclase sterol biosynthetic pathway with its substrate in animals, yeast and higher plants. Characterization of these three new components involved in C-4 demethylation participates to the completion of the molecular inventory of sterol synthesis in higher plants.
authors.affiliation: Institut de Biologie Moléculaire des Plantes, UPR-CNRS 2357, 28 rue Goethe, 67083 Strasbourg, France. alain.rahier@ibmp-cnrs.unistra.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Rahier
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D017360:Arabidopsis / Q000201:enzymology; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D004791:Enzyme Inhibitors; D008745:Methylation; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010840:Phytosterols / Q000378:metabolism*; D010944:Plants / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D010840:Phytosterols; D015096:3-Hydroxysteroid Dehydrogenases; D013250:Steroid Hydroxylases; D002262:Carboxy-Lyases