1bda: Difference between revisions
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==CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)== | |||
<StructureSection load='1bda' size='340' side='right'caption='[[1bda]], [[Resolution|resolution]] 3.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1bda]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BDA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.35Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2Z0:N-{[5-(DIMETHYLAMINO)NAPHTHALEN-2-YL]SULFONYL}-L-ALPHA-GLUTAMYL-N-[(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-(CHLOROACETYL)BUTYL]GLYCINAMIDE'>2Z0</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bda OCA], [https://pdbe.org/1bda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bda RCSB], [https://www.ebi.ac.uk/pdbsum/1bda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bda ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TPA_HUMAN 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 == | |||
[https://www.uniprot.org/uniprot/TPA_HUMAN 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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bd/1bda_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bda ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:9305622</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1bda" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Plasminogen activator|Plasminogen activator]] | *[[Plasminogen activator|Plasminogen activator]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bode | [[Category: Bode W]] | ||
[[Category: Engh | [[Category: Engh RA]] | ||
[[Category: Renatus | [[Category: Renatus M]] | ||
Latest revision as of 07:24, 17 October 2024
CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH DANSYL-EGR-CMK (DANSYL-GLU-GLY-ARG CHLOROMETHYL KETONE)
Structural highlights
DiseaseTPA_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. FunctionTPA_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 PubMedTissue 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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