1wbg

Active site thrombin inhibitors

spinqualitylabelsall models 1wbg, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1wbg 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: DMS, L03 NonStd Res: TYS Related: 1a2c, 1a3b, 1a3e, 1a46, 1a4w, 1a5g, 1a61, 1abi, 1abj, 1ad8, 1ae8, 1afe, 1aht, 1ai8, 1aix, 1awf, 1awh, 1ay6, 1b5g, 1b7x, 1ba8, 1bb0, 1bcu, 1bhx, 1bmm, 1bmn, 1bth, 1c1u, 1c1v, 1c1w, 1c4u, 1c4v, 1c4y, 1c5l, 1c5n, 1c5o, 1ca8, 1d3d, 1d3p, 1d3q, 1d3t, 1d4p, 1d6w, 1d9i, 1de7, 1dit, 1dm4, 1doj, 1dwb, 1dwc, 1dwd, 1dwe, 1dx5, 1e0f, 1eb1, 1eoj, 1eol, 1fpc, 1fph, 1g30, 1g32, 1g37, 1ghv, 1ghw, 1ghx, 1ghy, 1gj4, 1gj5, 1h8d, 1h8i, 1hag, 1hah, 1hai, 1hao, 1hap, 1hbt, 1hdt, 1hgt, 1hlt, 1hut, 1hxe, 1hxf, 1ihs, 1iht, 1jmo, 1jou, 1jwt, 1kts, 1ktt, 1lhc, 1lhd, 1lhe, 1lhf, 1lhg, 1mh0, 1mu6, 1mu8, 1mue, 1nm6, 1no9, 1nrn, 1nro, 1nrp, 1nrq, 1nrr, 1nt1, 1nu7, 1nu9, 1ny2, 1nzq, 1o0d, 1o2g, 1o5g, 1ook, 1oyt, 1p8v, 1ppb, 1qbv, 1qhr, 1qj1, 1qj6, 1qj7, 1qur, 1qvh, 1rd3, 1riw, 1sb1, 1sfq, 1sg8, 1sgi, 1shh, 1sl3, 1sr5, 1ta2, 1ta6, 1tb6, 1tbz, 1thp, 1thr, 1ths, 1tmb, 1tmt, 1tmu, 1tom, 1tq0, 1tq7, 1uma, 1uvs, 1vr1, 2hgt, 2hnt, 2hpp, 2hpq, 2thf, 4thn, 5gds, 7kme, 8kme, 1k21, 1k22, 1nrs, 1vzq, 1w7g, 1way, 3hat, 3htc, 4htc 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. [HIRV2_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 Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper. Fragment-based lead discovery using X-ray crystallography.,Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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