Crystal Structure of Ethylbenzene Dehydrogenase from Aromatoleum aromaticum

• Published in: Structure (London) 2006-09, Vol.14 (9), p.1377-1388
• Main Authors: Kloer, Daniel P., Hagel, Corina, Heider, Johann, Schulz, Georg E.
• Format: Article
• Language: English
• Subjects: Crystallography; Models, Molecular; Oxidoreductases - chemistry; Protein Conformation; Proteobacteria - enzymology
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2006.07.001

Anaerobic 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.