Twists in catalysis: Alternating conformations of Escherichia coli thioredoxin reductase

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 nicotin amide adenine dinucleotide phosphate) domains. We describe the structure of the ftavin-reducing conformation of E. coli TrxR at a resolution of 3.0 an gstroms. The orientation of the two domains permits reduction of FAD by NAD PH and oxidation of the enzyme dithiol by the protein substrate, thioredoxi n. The alternate conformation, described by Kuriyan and co-workers, permits internal transfer of reducing equivalents from reduced FAD to the active-s ite disulfide. Comparison of these structures demonstrates that switching b etween the two conformations involves a "ball-and-socket" motion in which t he pyridine nucleotide-binding domain rotates by 67 degrees.