1bda | pdb_00001bda

CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)

spinqualitylabelsall models 1bda, resolution 3.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1bda is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2Z0 Activity: T-plasminogen activator, with EC number 3.4.21.68 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [TPA_HUMAN] Note=Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism. Function [TPA_HUMAN] Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration. 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 Tissue type plasminogen activator (tPA) is the physiological initiator of fibrinolysis, activating plasminogen via highly specific proteolysis; plasmin then degrades fibrin with relatively broad specificity. Unlike other chymotrypsin family serine proteinases, tPA is proteolytically active in a single-chain form. This form is also preferred for therapeutic administration of tPA in cases of acute myocardial infarction. The proteolytic cleavage which activates most other chymotrypsin family serine proteinases increases the catalytic efficiency of tPA only 5- to 10-fold. The X-ray crystal structure of the catalytic domain of recombinant human single-chain tPA shows that Lys156 forms a salt bridge with Asp194, promoting an active conformation in the single-chain form. Comparisons with the structures of other serine proteinases that also possess Lys156, such as trypsin, factor Xa and human urokinase plasminogen activator (uPA), identify a set of secondary interactions which are required for Lys156 to fulfil this activating role. These findings help explain the anomalous single-chain activity of tPA and may suggest strategies for design of new therapeutic plasminogen activators. Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA.,Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W EMBO J. 1997 Aug 15;16(16):4797-805. PMID:9305622 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Plasminogen activator

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