Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X.
The gamma-carboxyglutamic acid (Gla) domain of blood coagulation factors is responsible for Ca2+-dependent phospholipid membrane binding. Factor X-binding protein (X-bp), an anticoagulant protein from snake venom, specifically binds to the Gla domain of factor X. The crystal structure of X-bp in complex with the Gla domain peptide of factor X at 2.3-A resolution showed that the anticoagulation is based on the fact that two patches of the Gla domain essential for membrane binding are buried in the complex formation. The Gla domain thus is expected to be a new target of anticoagulant drugs, and X-bp provides a basis for designing them. This structure also provides a membrane-bound model of factor X.
Mizuno
H
H
Department of Biotechnology, National Institute of Agrobiological Resources, Tsukuba, Ibaraki 305-8602, Japan. mizuno@nias.affrc.go.jp
Fujimoto
Z
Z
Atoda
H
H
Morita
T
T
D015055:1-Carboxyglutamic Acid; D017836:Agkistrodon; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D002417:Cattle; D003435:Crotalid Venoms / Q000737:chemistry; D018360:Crystallography, X-Ray / Q000379:methods; D005170:Factor X / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D003435:Crotalid Venoms; C431277:factor X-binding protein, Deinagkistrodon acutus; D015055:1-Carboxyglutamic Acid; D005170:Factor X