title: The interactions of phenytoin and its binding site in DI-S6 segment of Na+ channel voltage-gated peptide by NMR spectroscopy and molecular modeling study.
abstract: Nuclear magnetic resonance (NMR) spectra of a model peptide (BL-DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL-DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na+-channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide- and alpha-protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 3(10)-helical structure for BL-DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans-7, Leu-8, Val-11, and Val-12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C-terminal residues Ala-11 and Val-12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn-7 periphery and stabilizing the phenyl portion deep insertion into the peptide.
authors.affiliation: Chemistry Division, Center for General Education, Chang Gung University, Tao-Yuan, Taiwan. blou@mail.cgu.edu.tw
authors.forename: B-S
authors.initials: BS
authors.lastname: Lou
authors.forename: T-H
authors.initials: TH
authors.lastname: Lin
authors.forename: C-Z
authors.initials: CZ
authors.lastname: Lo
mesh_terms: D000927:Anticonvulsants / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010672:Phenytoin / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D011522:Protons
chemical_list: D000927:Anticonvulsants; C504267:BL-DIS6 peptide; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011522:Protons; D010672:Phenytoin