Properties of the Thioredoxin Fold Superfamily Are Modulated by a Single Amino Acid ResidueS

The ubiquitous thioredoxin fold proteins catalyze oxidation, reduction, or disulfide exchange reactions depending on their redox properties. They also play vital roles in protein folding, redox control, and disease. Here, we have shown that a single residue strongly modifies both the redox propertie...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 284; no. 15; pp. 10150 - 10159
Main Authors:	Ren, Guoping, Stephan, Daniel, Xu, Zhaohui, Zheng, Ying, Tang, Danming, Harrison, Rosemary S., Kurz, Mareike, Jarrott, Russell, Shouldice, Stephen R., Hiniker, Annie, Martin, Jennifer L., Heras, Begoña, Bardwell, James C. A.
Format:	Journal Article
Language:	English
Published:	American Society for Biochemistry and Molecular Biology 10-04-2009
Subjects:	Enzyme Catalysis and Regulation
Online Access:	Get full text
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Summary:	The ubiquitous thioredoxin fold proteins catalyze oxidation, reduction, or disulfide exchange reactions depending on their redox properties. They also play vital roles in protein folding, redox control, and disease. Here, we have shown that a single residue strongly modifies both the redox properties of thioredoxin fold proteins and their ability to interact with substrates. This residue is adjacent in three-dimensional space to the characteristic C XX C active site motif of thioredoxin fold proteins but distant in sequence. This residue is just N-terminal to the conservative cis -proline. It is isoleucine 75 in the case of thioredoxin. Our findings support the conclusion that a very small percentage of the amino acid residues of thioredoxin-related proteins are capable of dictating the functions of these proteins.
Bibliography:	An Investigator of the Howard Hughes Medical Institute. To whom correspondence may be addressed. Tel.: 734-764-8028; E-mail: jbardwel@umich.edu. To whom correspondence may be addressed. Tel.: 61-7-3346-2016; Fax: 61-7-3346-2101; E-mail: b.heras@imb.uq.edu.au. The on-line version of this article (available at http://www.jbc.org) contains supplemental Experimental Procedures, Figs. S1-S4, and Tables S1-S3. Author's Choice—Final version full access. Recipient of a University of Queensland Postdoctoral Research Fellowship. Recipient of an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship. The atomic coordinates and structure factors (code 3DYR) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/). This work was supported, in whole or in part, by a grant from the National Institutes of Health (to J. C. A. B.). This work was also supported by the Australian Research Council (to B. H. and J. L. M.) and a University of Queensland Early Career Research Award (to B. H.).
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.M809509200