Journalartikel

Jahr der Veröffentlichung: 2009

Seiten: 890-U120

Zeitschrift: Nature Structural & Molecular Biology

Bandnummer: 16

Heftnummer: 8

ISSN: 1545-9993

eISSN: 1545-9985

Open Access Status: Green

DOI Link: https://doi.org/10.1038/nsmb.1627

Verlag: Nature Research

Abstract: 
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.

Harvard-Zitierstil: Perez-Jimenez, R., Li, J., Kosuri, P., Sanchez-Romero, I., Wiita, A., Rodriguez-Larrea, D., et al. (2009) Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy, Nature Structural & Molecular Biology, 16(8), pp. 890-U120. https://doi.org/10.1038/nsmb.1627

APA-Zitierstil: Perez-Jimenez, R., Li, J., Kosuri, P., Sanchez-Romero, I., Wiita, A., Rodriguez-Larrea, D., Chueca, A., Holmgren, A., Miranda-Vizuete, A., Becker, K., Cho, S., Beckwith, J., Gelhaye, E., Jacquot, J., Gaucher, E., Sanchez-Ruiz, J., Berne, B., & Fernandez, J. (2009). Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy. Nature Structural & Molecular Biology. 16(8), 890-U120. https://doi.org/10.1038/nsmb.1627