TY - JOUR
T1 - A Redox-controlled Molecular Switch Revealed by the Crystal Structure of a Bacterial Heme PAS Sensor
AU - Kurokawa, Hirofumi
AU - Lee, Dong Sun
AU - Watanabe, Miki
AU - Sagami, Ikuko
AU - Mikami, Bunzo
AU - Raman, C. S.
AU - Shimizu, Toru
PY - 2004/5/7
Y1 - 2004/5/7
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M314199200
DO - 10.1074/jbc.M314199200
M3 - Article
C2 - 14982921
AN - SCOPUS:2442624510
VL - 279
SP - 20186
EP - 20193
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 19
ER -