Silvia Arredondo silvia[at]che.utexas.edu

Academic Background

B.E., Chemical Engineering, The City College of New York, CUNY

 

Research Description
Engineering and Characterization of Bacterial Disulfide Isomerases
The general objective of my research projects is the engineering of the E. coli disulfide bond formation machinery for the efficient folding of heterologous proteins containing complex disulfide bond patterns. Particularly, because the rearrangement of non native disulfide bonds represents the rate limiting step during the folding of multidisulfide containing proteins, my objective is to develop an enhanced disulfide bond isomerase. The questions I have been exploring are (i) what are the basic components of an isomerase? And, can we construct an efficient artificial isomerase based on these basic elements? (ii) Are two catalytic domains strictly necessary for successful isomerization in vivo? and (iii) What are the essential residues in the isomerase-substrate binding interaction? While engineering an optimized isomerase in bacteria is the goal in mind, we also consider fundamental to further our understanding of the basic scientific principles involved in disulfide bond formation and isomerization and we hope to accomplish both by answering the above questions.

Publications:
Arredondo, S., Segatori, L., Gilbert, H., and Georgiou, G. (2008) De novo Design and Evolution of Artificial Disulfide Isomerase Enzymes Analogous to the Bacterial DsbC. J Biol Chem, (submitted)

Segatori, L., Murphy, L., Arredondo, S., Kadokura, H., Gilbert, H., Beckwith, J. and Georgiou, G. (2006) Conserved role of the linker alpha-helix of the bacterial disulfide isomerase DsbC in the avoidance of misoxidation by DsbB. J Biol Chem, 281, 4911-4919.