A proton wire and water channel revealed in the crystal structure of isatin hydrolase

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  • Kaare Bjerregaard-Andersen, Denmark
  • Theis Sommer, Oslo Universitet, Norway
  • Jan Kristian Jensen
  • Bjarne Jochimsen, Denmark
  • Michael Etzerodt
  • Jens Preben Morth, Oslo Universitet, Denmark
The high resolution crystal structures of isatin hydrolase from Labrenzia aggregata in the apo and the product state, are described. These are the first structures of a functionally characterized metal-dependent hydrolase of this fold. Isatin hydrolase converts isatin to isatinate and belongs to a novel family of metalloenzymes that include the bacterial kynurenine formamidase. The product state, mimicked by bound thioisatinate, reveals a water molecule that bridges the thioisatinate to a proton wire in an adjacent water channel and thus allows the proton released by the reaction to escape only when the product is formed. The functional proton wire present in IH-b represents a unique catalytic feature common to all hydrolases is here trapped and visualized for the first time. The local molecular environment required to coordinate thioisatinate allows stronger and more confident identification of orthologous genes encoding isatin hydrolases within the prokaryotic kingdom. The isatin hydrolase orthologues found in human gut bacteria raise the question as to whether the indole-3-acetic acid degradation pathway is present in human gut flora.
Original languageEnglish
JournalJournal of Biological Chemistry
Pages (from-to)21351-21359
Number of pages9
Publication statusPublished - 1 Aug 2014

    Research areas

  • isatin hydrolase, proton wire, enzyme structure, metalloenzyme, IAA degradation

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