| Literature DB >> 15642260 |
E Allen Sickmier1, Dimitris Brekasis, Shanthi Paranawithana, Jeffrey B Bonanno, Mark S B Paget, Stephen K Burley, Clara L Kielkopf.
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 A 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" alpha 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.Entities:
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Year: 2005 PMID： 15642260 DOI： 10.1016/j.str.2004.10.012
Source DB: PubMed Journal: Structure ISSN： 0969-2126 Impact factor: 5.006