title: Properties of the thioredoxin fold superfamily are modulated by a single amino acid residue.
abstract: 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 CXXC 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.
authors.affiliation: Howard Hughes Medical Institute, Departments of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Ren
authors.forename: Daniel
authors.initials: D
authors.lastname: Stephan
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Danming
authors.initials: D
authors.lastname: Tang
authors.forename: Rosemary S
authors.initials: RS
authors.lastname: Harrison
authors.forename: Mareike
authors.initials: M
authors.lastname: Kurz
authors.forename: Russell
authors.initials: R
authors.lastname: Jarrott
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Shouldice
authors.forename: Annie
authors.initials: A
authors.lastname: Hiniker
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martin
authors.forename: Begoña
authors.initials: B
authors.lastname: Heras
authors.forename: James C A
authors.initials: JC
authors.lastname: Bardwell
mesh_terms: D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007532:Isoleucine / Q000737:chemistry; D007700:Kinetics; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013879:Thioredoxins / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; D007532:Isoleucine; D013879:Thioredoxins; D011392:Proline; D010088:Oxidoreductases; D019704:Protein Disulfide-Isomerases; C526648:dsbA protein, E coli