Twists in Catalysis: Alternating Conformations of Escherichia coli Thioredoxin Reductase
Brett W. Lennon,1
Charles H. Williams Jr.,23
Martha L. Ludwig12*
In thioredoxin reductase (TrxR) from Escherichia
coli, cycles of reduction and reoxidation of the flavin adenine
dinucleotide (FAD) cofactor depend on rate-limiting rearrangements of
the FAD and NADPH (reduced form of nicotinamide adenine dinucleotide
phosphate) domains. We describe the structure of the flavin-reducing
conformation of E. coli TrxR at a resolution of 3.0 angstroms. The orientation of the two domains permits reduction of FAD
by NADPH and oxidation of the enzyme dithiol by the protein substrate,
thioredoxin. The alternate conformation, described by Kuriyan and
co-workers, permits internal transfer of reducing equivalents from
reduced FAD to the active-site disulfide. Comparison of these
structures demonstrates that switching between the two conformations
involves a "ball-and-socket" motion in which the pyridine
nucleotide-binding domain rotates by 67 degrees.
1 Biophysics Research Division,
2 Department of Biological Chemistry, University of
Michigan, Ann Arbor, MI 48109, USA.
3 Department of
Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
*
To whom correspondence should be addressed. E-mail:
mlludwig{at}umich.edu
