Understanding the conformation and reaction pathways of disulfide bonds


Disulfide bonds play crucial roles in biology. Intramolecular disulfide bonds between cysteine residues stabilise folded conformations in proteins, contribute to enzyme and antibiotic activities, and very recently they have been found to act as conformational switches that can activate biological activity in proteins. However, very limited accurate information is available on the conformations around disulfide bonds sampled by proteins and their preferences and influence on reactivity. The aim of this project is to characterise the possible conformational arrangements and reaction pathways of molecular systems involving disulfide bonds by using a combination of advanced high-resolution spectroscopic and biophysical techniques. 


M. E. Sanz, S. Blanco, J. C. López, J. L. Alonso, “Rotational probes of six conformers of neutral cysteine”, Angew. Chem. Int. Ed., 47, 6216 (2008).


D. Loru, I. Peña, J.L. Alonso, M. E. Sanz, “Intramolecular interactions in the polar headgroup of sphingosine: serinol”, Chem.Comm., 47, 6216 (2016).


I. Peña, M. E. Sanz, J. C. López, J. L. Alonso, “Preferred conformers of proteinogenic glutamic acid”, J. Am. Chem. Soc, 134, 2305 (2012).


Garcia-Manyes, S. et al.«Contrasting the individual reactive pathways in protein unfolding and disulfide bond reduction observed within a single protein»,  Journal of the American Chemical Society, 133 (9), 3104 (2011)


Garcia-Manyes, S; Liang, J.; Szoszkiewicz, R.; Kuo, T.; Fernandez, J.M.; «Force-activated reactivity switch in a bimolecular chemical reaction»,  Nature Chemistry, 3, 236 (2009).

Biological Areas:

Cell Biology


Molecules, cells and industrial biotechnology