Impact of sequence and structure on the redox properties of thioredoxin and glutaredoxin

BIOL 50

Sanghamitra Mitra, smitra@bu.edu1, Hector H. Hernandez2, Catherine L. Drennan2, and Sean J. Elliott1. (1) Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, (2) Department of chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139
Thioredoxin (Trx) and glutaredoxin (Grx) belong to Trx superfamily of thiol-disulfide oxidoreductases. These are small soluble proteins sharing a single -CXXC- motif that contains the cysteine residues participating in the 2e-/2H+ chemistry. It has been suggested that the nature of the amino acids in the motif determines the reduction potential of the resulting disulfide. We have installed -CXXC- sequences of known oxidizing and reducing disulfide bonds in an identical Trx protein fold and have used protein film voltammometry (PFV) to determine their reduction potentials. Our data reveals a connection between sequence and redox potentials. Recently, human Grx2 in its inactive dimeric form was found to contain an iron-sulfur cluster and was proposed to function as a redox sensor. We have produced the iron-sulfur loaded form of the protein, and have used PFV to induce and monitor the impact of oxidative stress on the iron-sulfur cluster in a recombinant human Grx2.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007