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A redox-controlled molecular switch revealed by the crystal structure of a bacterial heme PAS sensor.

Authors
  • Kurokawa, Hirofumi
  • Lee, Dong-Sun
  • Watanabe, Miki
  • Sagami, Ikuko
  • Mikami, Bunzo
  • Raman, C S
  • Shimizu, Toru
Type
Published Article
Journal
The Journal of biological chemistry
Publication Date
May 07, 2004
Volume
279
Issue
19
Pages
20186–20193
Identifiers
PMID: 14982921
Source
Medline
License
Unknown

Abstract

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 Fe(3+) and active Fe(2+) forms at 1.32 and 1.9 A 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.

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