Molecular dynamics simulations of thioredoxin with S-glutathiolated cysteine-73.
Thioredoxin-1 (Trx) becomes inactive when cysteine-73 forms a mixed disulfide with glutathione. This reversible S-glutathiolation may serve as a regulatory mechanism. However, molecular basis for the glutathiolation-induced inhibition has not been established due to the lack of its structure. Molecular dynamics (MD) simulations were performed with Gromacs to obtain structural information on glutathiolated Trx. Glutathiolation did not cause a large change in overall shape of Trx although small local changes in the secondary structures were evident. The glutathione moiety was much more flexible than the peptide and spanned a large conformational space. It remained very close to the active site for a large part of the simulation time. Therefore inhibition of Trx by glutathiolation appears to be due to steric hindrance imposed by the covalently attached glutathione.
Han
Sanghwa
S
Department of Biochemistry and Institute for Life Sciences, Kangwon National University, Chunchon 200-701, South Korea. hansh@kangwon.ac.kr
D001665:Binding Sites; D003198:Computer Simulation; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism
D013879:Thioredoxins; D005978:Glutathione; D003545:Cysteine