1bda
From Proteopedia
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|PDB= 1bda |SIZE=350|CAPTION= <scene name='initialview01'>1bda</scene>, resolution 3.35Å | |PDB= 1bda |SIZE=350|CAPTION= <scene name='initialview01'>1bda</scene>, resolution 3.35Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CH2:METHYLENE GROUP'>CH2</scene> | + | |LIGAND= <scene name='pdbligand=CH2:METHYLENE+GROUP'>CH2</scene>, <scene name='pdbligand=DSY:5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC+ACID'>DSY</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/T-plasminogen_activator T-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.68 3.4.21.68] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/T-plasminogen_activator T-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.68 3.4.21.68] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bda OCA], [http://www.ebi.ac.uk/pdbsum/1bda PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bda RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Plasminogen activator deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173370 173370]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Engh, R A.]] | [[Category: Engh, R A.]] | ||
[[Category: Renatus, M.]] | [[Category: Renatus, M.]] | ||
| - | [[Category: CH2]] | ||
[[Category: fibrinolytic enzyme]] | [[Category: fibrinolytic enzyme]] | ||
[[Category: plasminogen activator]] | [[Category: plasminogen activator]] | ||
[[Category: trypsin like serine protease]] | [[Category: trypsin like serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:58:37 2008'' |
Revision as of 15:58, 30 March 2008
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| , resolution 3.35Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | T-plasminogen activator, with EC number 3.4.21.68 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)
Overview
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.
About this Structure
1BDA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 18:58:37 2008
