Contribution of ring strain to catalysis: Comparison of cyclic and acyclic forms of octapeptides as substrates for high Mr thioredoxin reductases

BIOL 187

Brian M. Lacey, blacey@uvm.edu, Stevenson Flemer Jr., sflemer@uvm.edu, and Robert J. Hondal, Robert.Hondal@uvm.edu. Department of Biochemistry, University of Vermont, Given Building, 89 Beaumont Avenue, Burlington, VT 05405
Thioredoxin reductase (TR) is an essential part of the thioredoxin system, which functions to maintain cellular redox homeostasis. High Mr TR's are highly conserved and have a C-terminal 16 amino acid extension, compared to the related enzyme glutathione reductase (GR), which contains an additional redox center. TR's are all capable of reducing thioredoxin, though each utilizes a different C-terminal tetrapeptide redox motif of form: AA1-Cys2-Cys3-AA4 or AA1-Cys2-Sec3-AA4. This motif forms a vicinal disulfide or selenylsulfide bond, resulting in an eight-membered ring, which must be opened during the catalytic cycle. We show that truncated enzymes (missing their C-terminal 8 amino acids) are capable of reducing their cognate peptide in a manner analogous to GR and oxidized glutathione (GSSG). Peptides in the cyclic or acyclic form have been synthesized to investigate the contribution of the ring in the ring opening step.

 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

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