A Redox-controlled Molecular Switch Revealed by the Crystal Structure of a Bacterial Heme PAS Sensor

Hirofumi Kurokawa, Dong Sun Lee, Miki Watanabe, Ikuko Sagami, Bunzo Mikami, C. S. Raman, Toru Shimizu

Research output: Contribution to journalArticlepeer-review

151 Citations (Scopus)


PAS domains, which have been identified in over 1100 proteins from all three kingdoms of life, convert various input stimuli into signals that propagate to downstream components by modifying protein-protein interactions. One such protein is the Escherichia coli redox sensor, Ec DOS, a phosphodiesterase that degrades cyclic adenosine monophosphate in a redox-dependent manner. Here we report the crystal structures of the heme PAS domain of Ec DOS in both inactive Fe3+ and active Fe2+ forms at 1.32 and 1.9 Å resolution, respectively. The protein folds into a characteristic PAS domain structure and forms a homodimer. In the Fe 3+ form, the heme iron is ligated to a His-77 side chain and a water molecule. Heme iron reduction is accompanied by heme-ligand switching from the water molecule to a side chain of Met-95 from the FG loop. Concomitantly, the flexible FG loop is significantly rigidified, along with a change in the hydrogen bonding pattern and rotation of subunits relative to each other. The present data led us to propose a novel redox-regulated molecular switch in which local heme-ligand switching may trigger a global "scissor-type" subunit movement that facilitates catalytic control.

Original languageEnglish
Pages (from-to)20186-20193
Number of pages8
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - 2004 May 7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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