Homology modeling and molecular dynamics simulation of human prothrombin fragment 1.
The crystallographic structure of bovine prothrombin fragment 1 bound with calcium ions was used to construct the corresponding human prothrombin structure (hf1/Ca). The model structure was refined by molecular dynamics to estimate the average solution structure. Accommodation of long-range ionic forces was essential to reach a stable solution structure. The gamma-carboxyglutamic acid (Gla) domain and the kringle domain of hf1/Ca independently equilibrated. Likewise, the hydrogen bond network and the calcium ion coordinations were well preserved. A discussion of the phospholipid binding of the vitamin K-dependent coagulation proteins in the context of the structure and mutational data of the Gla domain is presented.
Li
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L
Department of Chemistry, University of North Carolina, Chapel Hill 27599-3290, USA.
Darden
T
T
Foley
C
C
Hiskey
R
R
Pedersen
L
L
D015055:1-Carboxyglutamic Acid / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001779:Blood Coagulation Factors / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D018082:Kringles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011516:Prothrombin / Q000737:chemistry* / Q000378:metabolism; D017385:Sequence Homology; D014812:Vitamin K / Q000494:pharmacology
D001779:Blood Coagulation Factors; D010446:Peptide Fragments; D010743:Phospholipids; D011498:Protein Precursors; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid; C029733:prothrombin fragment 1; D011516:Prothrombin; D002118:Calcium