1vzq
Complex of thrombin with designed inhibitor 7165
Structural highlights
DiseaseTHRB_HUMAN Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:613679. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.[13] Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:188050. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:614390. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.[14] FunctionTHRB_HUMAN Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.[15] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA human prothrombin cDNA has been engineered to obtain a cDNA coding for a secreted form of human prethrombin-2. The secreted prethrombin-2 has been produced in a mammalian expression system using DXB11 cells, a mutant strain of CHO cells in which the dihydrofolate reductase gene has been deleted, and an expression vector carrying the dihydrofolate reductase cDNA. Methotrexate-induced gene amplification favored an efficient production of the recombinant protein which accumulated in the culture medium of the DXB11 cells. Growth in suspension of the stable transformants in an airlift fermenter resulted in the production of 25 mg/L recombinant prethrombin-2. The recombinant protein was purified using single-step affinity chromatography on a recombinant-hirudin column and activated by agarose gel-immobilized ecarin. All purified recombinant prethrombin-2 was activated and the generated recombinant thrombin showed catalytic properties identical to those of plasma-derived alpha-thrombin. This expression system can be used to prepare mutants of prethrombin-2 for structure-function studies investigating thrombin interactions with substrate proteins, inhibitors, and cell membranes. Stable expression and purification of a secreted human recombinant prethrombin-2 and its activation to thrombin.,Russo G, Gast A, Schlaeger EJ, Angiolillo A, Pietropaolo C Protein Expr Purif. 1997 Jul;10(2):214-25. PMID:009226718[16] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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