title: Molecular dynamics calculations of wild type vs. mutant protein C: relationship between binding affinity to endothelial cell protein C receptor and hereditary disease.
abstract: Molecular dynamics simulations of the protein C gamma-carboxyglutamic acid (Gla) domain and endothelial cell protein C receptor (EPCR) complex were performed to determine the effect of a hereditary disease, which results in a mutation (Gla 25 --> Lys) in the protein C Gla domain. Our results suggest that the Gla 25 --> Lys mutation causes a significant reduction in the binding force between protein C Gla domain and EPCR due to destabilization of the helix structure of EPCR and displacement of a Ca2+ ion.
authors.affiliation: VALWAY Technology Center, NEC Soft, Ltd., Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shikamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuno
authors.forename: Tadashi
authors.initials: T
authors.lastname: Murase
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishii
authors.forename: Toru
authors.initials: T
authors.lastname: Nakabayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ieko
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizukami
authors.forename: Sumiyoshi
authors.initials: S
authors.lastname: Naitoh
authors.forename: Mika
authors.initials: M
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Tarumi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kaneko
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000235:genetics; D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000378:metabolism*; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000235:genetics; D008957:Models, Genetic; D008958:Models, Molecular; D011485:Protein Binding; D011486:Protein C / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface; D015055:1-Carboxyglutamic Acid; D008239:Lysine