Crystal Structure of Ethylbenzene Dehydrogenase from Aromatoleum aromaticum

SummaryAnaerobic degradation of hydrocarbons was discovered a decade ago, and ethylbenzene dehydrogenase was one of the first characterized enzymes involved. The structure of the soluble periplasmic 165 kDa enzyme was established at 1.88 Å resolution. It is a heterotrimer. The α subunit contains the catalytic center with a molybdenum held by two molybdopterin-guanine dinucleotides, one with an open pyran ring, and an iron-sulfur cluster with a histidine ligand. During catalysis, electrons produced by substrate oxidation are transferred to a heme in the γ subunit and then presumably to a separate cytochrome involved in nitrate respiration. The β subunit contains four iron-sulfur clusters and is structurally related to ferredoxins. The γ subunit is the first known protein with a methionine and a lysine as axial heme ligands. The catalytic product was modeled into the active center, showing the reaction geometry. A mechanism consistent with activity and inhibition data of ethylbenzene-related compounds is proposed.