Hector Hernandez - Thioredoxin Reductase from Thermoplasma acidophilum: A New Twist on Redox Regulation†,‡

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      Publication Details (including relevant citation   information):

      Hernandez, Hector H., Jaquez, Orlando A., Hamill, Michael J.,   Elliott, Sean J., Drennan, Catherine L. Biochemistry  2008 47 (37) 9728-9737

      Abstract: Thioredoxin reductases (TrxRs)   regulate the intracellular redox environment by using NADPH to   provide reducing equivalents for thioredoxins (Trxs). Here we   present the cloning and biochemical characterization of a   putative TrxR (Ta0984) and a putative Trx (Ta0866) from   Thermoplasma acidophilum. Our data identify Ta0866 as a Trx   through its capacity to reduce insulin and be reduced by   Escherichia coli TrxR in a NADPH-dependent manner. Our data also   establish Ta0984 as a TrxR due to its ability to reduce T.   acidophilum Trx (taTrx), although not in a NADPH- or   NADH-dependent manner. To explore the apparent inability of   taTrxR to use NADPH or NADH as a reductant, we carried out a   complete electrochemical characterization, which suggests that   redox potential is not the source of this nonreactivity [Hamill   et al. (2008) Biochemistry 47, 9738?9746]. Turning to   crystallographic analysis, a 2.35 Å resolution structure of   taTrxR, also presented here, shows that despite the overall   structural similarity to the well-characterized TrxR from E. coli   (RMSD 1.30 Å2 for chain A), the ?NADPH binding pocket? is not   conserved. E. coli TrxR residues implicated in NADPH binding,   H175, R176, R177, and R181, have been substituted with E185,   Y186, M187, and M191 in the ta protein. Thus, we have identified   a Trx and TrxR protein system from T. acidophilum for which the   TrxR shares overall structural and redox properties with other   TrxRs but lacks the appropriate binding motif to use the standard   NADPH reductant. Our discovery of a TrxR that does not use NADPH   provides a new twist in redox regulation.

      Address (URL): http://dx.doi.org/10.1021/bi8006753