Succinate complex crystal structures of the α-ketoglutarate-dependent dioxygenase AtsK: Steric aspects of enzyme self-hydroxylation

Ilka Müller, Claudia Stückl, James Wakeley, Michael Kertesz, Isabel Usón

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The alkylsulfatase AtsK from Pseudomonas putida S-313 is a member of the non-heme iron(II)-α-ketoglutarate-dependent dioxygenase superfamily. In the initial step of their catalytic cycle, enzymes belonging to this widespread and versatile family coordinate molecular oxygen to the iron center in the active site. The subsequent decarboxylation of the cosubstrate α-ketoglutarate yields carbon dioxide, succinate, and a highly reactive ferryl (IV) species, which is required for substrate oxidation via a complex mechanism involving the transfer of radical species. Non-productive activation of oxygen may lead to harmful side reactions; therefore, such enzymes need an effective built-in protection mechanism. One of the ways of controlling undesired side reactions is the self-hydroxylation of an aromatic side chain, which leads to an irreversibly inactivated species. Here we describe the crystal structure of the alkylsulfatase AtsK in complexes with succinate and with Fe(II)/succinate. In the crystal structure of the AtsK-Fe(II)-succinate complex, the side chain of Tyr 168 is coordinated to the iron, suggesting that Tyr 168 is the target of enzyme self-hydroxylation. This is the first structural study of an Fe(II)-α-ketoglutarate-dependent dioxygenase that presents an aromatic side chain coordinated to the metal center, thus allowing structural insight into this protective mechanism of enzyme self-inactivation.
    Original languageEnglish
    Pages (from-to)5716-5723
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume280
    Issue number7
    DOIs
    Publication statusPublished - 18 Feb 2005

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