Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 16, Issue 8, Pages 890-U120Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1627
Keywords
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Funding
- US National Institutes of Health [HL66030, HL61228, GMO55090, GM43340]
- Columbia University
- Spanish Ministry of Education and Science [BIO2006-07332]
- FEDER Funds
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Thioredoxins (Trxs) are oxidoreductase enzymes, present in all organisms, that catalyze the reduction of disulfide bonds in proteins. By applying a calibrated force to a substrate disulfide, the chemical mechanisms of Trx catalysis can be examined in detail at the single-molecule level. Here we use single-molecule force-clamp spectroscopy to explore the chemical evolution of Trx catalysis by probing the chemistry of eight different Trx enzymes. All Trxs show a characteristic Michaelis-Menten mechanism that is detected when the disulfide bond is stretched at low forces, but at high forces, two different chemical behaviors distinguish bacterial-origin from eukaryotic-origin Trxs. Eukaryotic-origin Trxs reduce disulfide bonds through a single-electron transfer reaction (SET), whereas bacterial-origin Trxs show both nucleophilic substitution (S(N)2) and SET reactions. A computational analysis of Trx structures identifies the evolution of the binding groove as an important factor controlling the chemistry of Trx catalysis.
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