1bda

From Proteopedia

(Difference between revisions)

Revision as of 11:00, 2 August 2023

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

Structural highlights

1bda is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.35Å
Ligands:
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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W. Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA. EMBO J. 1997 Aug 15;16(16):4797-805. PMID:9305622 doi:10.1093/emboj/16.16.4797

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bda"

Categories: Homo sapiens | Large Structures | Bode W | Engh RA | Renatus M

@@ Line 3: / Line 3: @@
 <StructureSection load='1bda' size='340' side='right'caption='[[1bda]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bda]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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>
+<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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.35&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/T-plasminogen_activator T-plasminogen activator], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.68 3.4.21.68] </span></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.
+[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.
+[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]]
@@ Line 38: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: T-plasminogen activator]]
+[[Category: Bode W]]
-[[Category: Bode, W]]
+[[Category: Engh RA]]
-[[Category: Engh, R A]]
+[[Category: Renatus M]]
-[[Category: Renatus, M]]
-[[Category: Fibrinolytic enzyme]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Plasminogen activator]]
-[[Category: Trypsin like serine protease]]

1bda

From Proteopedia

Revision as of 11:00, 2 August 2023

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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