View source for 4dva


==The crystal structure of human urokinase-type plasminogen activator catalytic domain==
<StructureSection load='4dva' size='340' side='right'caption='[[4dva]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dva]] is a 1 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=4DVA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DVA 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]] 1.94&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4dva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dva OCA], [https://pdbe.org/4dva PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dva RCSB], [https://www.ebi.ac.uk/pdbsum/4dva PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dva ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity.

Rezymogenation of active urokinase induced by an inhibitory antibody.,Jiang L, Botkjaer KA, Andersen LM, Yuan C, Andreasen PA, Huang M Biochem J. 2013 Jan 1;449(1):161-6. doi: 10.1042/BJ20121132. PMID:23016918<ref>PMID:23016918</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4dva" style="background-color:#fffaf0;"></div>

==See Also==
*[[Urokinase 3D Structures|Urokinase 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Andersen LM]]
[[Category: Andreasen PA]]
[[Category: Botkjaer KA]]
[[Category: Huang M]]
[[Category: Jiang L]]
[[Category: Yuan C]]