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AvtorPotamitis, Konstantinos
Matsoukas, Minos-Timotheos
Tselios, Theodore V.
Mavromoustakos, Thomas Michael
Golič Grdadolnik, Simona
Naslov Conformational analysis of the MBP[sub]83-99 (Phe[sup]91) and MBP[sub]83-99 (Tyr[sup]91) peptide analogues and study of their interactions with the HLA-DR2 and human TCR receptors by using molecular dynamics / C. Potamitis ... [et al.]
Vrsta/vsebinatype of material članek - sestavni del
Fizični opisstr. 837-853 : Ilustr.
OpombeBibliografija: str. 851-853
Predmetne oznake (nekontrolirane)conformational analysis / myelin basic protein / molecular dynamics / binding motif / multiple sclerosis
PovzetekThe two new synthetic analogues of the MBP83-99 epitope substituted at Lys91 (primary TCR contact) with Phe [MBP83-99 (Phe91)] or Tyr [MBP83-99 (Tyr91)], have been structurally elucidated using 1D and 2D high resolution NMR studies. The conformational analysis of the two altered peptide ligands (APLs) has been performed and showed that they adopt a linear and extended conformation which is in agreement with the structural requirements of the peptides that interact with the HLA-DR2 and TCR receptors. In addition, Molecular Dynamics (MD) simulations of the two analogues in complex with HLA-DR2 (DRA, DRB1*1501) and TCR were performed. Similarities and differences of the binding motif of the two analogues were observed which provide a possible explanation of their biological activity. Their differences in the binding mode in comparison with the MBP83-99 epitope may also explain their antagonistic versus agonistic activity. The obtained results clearly indicate that substitutions in crucial amino acids (TCR contacts) in combination with the specific conformational characteristics of the MBP83-99 immunodominant epitope lead to an alteration of their biological activity. These results make the rational drug design intriguing since the biological activity is very sensitive to the substitution and conformation of the mutated MBP epitopes.
Glej publikacijo TI=Journal of computer-aided molecular design ISSN: 0920-654X.- Vol. 25, no. 9 (2011), str. 837-853

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