Molecular dynamics calculations of wild type vs. mutant protein C: relationship between binding affinity to endothelial cell protein C receptor and hereditary disease.
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.
Nakagawa
Takafumi
T
VALWAY Technology Center, NEC Soft, Ltd., Tokyo, Japan.
Shikamoto
Yasuo
Y
Mizuno
Hiroshi
H
Murase
Tadashi
T
Ishii
Hajime
H
Nakabayashi
Toru
T
Ieko
Masahiro
M
Mizukami
Kazuhiro
K
Naitoh
Sumiyoshi
S
Takeda
Mika
M
Tarumi
Takashi
T
Kaneko
Hiroki
H
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*
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