2jh5

Human Thrombin Hirugen Inhibitor complex

spinqualitylabelsall models 2jh5, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jh5 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 895, CA, NA NonStd Res: TYS Related: 2jh0, 2jh6 Activity: Thrombin, with EC number 3.4.21.5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [THRB_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. 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. 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. Function [THRB_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. [HIR3A_HIRME] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen. 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 PubMed Structure-based design (SBD) is a challenging endeavour since even localised SAR can hardly ever be explained by the variation of just one dominating factor. Here, we present a rare example where structural information combined with ab initio calculations clearly indicate that the observed difference in biological activity is dominated by conformational effects. The learnings discussed are successfully put to the test and have the potential to be of general use as a qualitative guide in SBD efforts. Sulfonamide-related conformational effects and their importance in structure-based design.,Senger S, Chan C, Convery MA, Hubbard JA, Shah GP, Watson NS, Young RJ Bioorg Med Chem Lett. 2007 May 15;17(10):2931-4. Epub 2007 Feb 16. PMID:17336062 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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