Abstract
The redox-sensing repressor Rex regulates transcription of respiratory genes in response to the intra cellular NADH/NAD + redox poise. As a step toward elucidating the molecular mechanism of NADH/NAD + sensing, the X-ray structure of Thermus aquaticus Rex (T-Rex) bound to effector NADH has been determined at 2.9 Å resolution. The fold of the C-terminal domain of T-Rex is characteristic of NAD(H)-dependent enzymes, whereas the N-terminal domain is similar to a winged helix DNA binding motif. T-Rex dimerization is primarily mediated by "domain-swapped" α helices. Each NADH molecule binds to the C-terminal domain near the dimer interface. In contrast to NAD(H)-dependent enzymes, the nicotinamide is deeply buried within a hydrophobic pocket that appears to preclude substrate entry. We show that T-Rex binds to the Rex operator, and NADH but not NAD + inhibits T-Rex/DNA binding activity. A mechanism for redox sensing by Rex family members is proposed by analogy with domain closure of NAD(H)-dependent enzymes.
Original language | English (US) |
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Pages (from-to) | 43-54 |
Number of pages | 12 |
Journal | Structure |
Volume | 13 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2005 |
Externally published | Yes |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology