4dw2
From Proteopedia
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| - | + | ==The crystal structure of uPA in complex with the Fab fragment of mAb-112== | |
| - | + | <StructureSection load='4dw2' size='340' side='right' caption='[[4dw2]], [[Resolution|resolution]] 2.97Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4dw2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DW2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DW2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dvb|4dvb]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLAU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dw2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dw2 RCSB], [http://www.ebi.ac.uk/pdbsum/4dw2 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[http://omim.org/entry/601709 601709]]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. | ||
| + | <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> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | <references | + | *[[Monoclonal Antibody|Monoclonal Antibody]] |
| + | *[[Urokinase|Urokinase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: U-plasminogen activator]] | [[Category: U-plasminogen activator]] | ||
| - | [[Category: Andersen, L M | + | [[Category: Andersen, L M]] |
| - | [[Category: Andreasen, P A | + | [[Category: Andreasen, P A]] |
| - | [[Category: Botkjaer, K A | + | [[Category: Botkjaer, K A]] |
| - | [[Category: Huang, M | + | [[Category: Huang, M]] |
| - | [[Category: Jiang, L | + | [[Category: Jiang, L]] |
| - | [[Category: Yuan, C | + | [[Category: Yuan, C]] |
[[Category: Antibody]] | [[Category: Antibody]] | ||
[[Category: Hydrolase-immune system complex]] | [[Category: Hydrolase-immune system complex]] | ||
Revision as of 11:05, 21 December 2014
The crystal structure of uPA in complex with the Fab fragment of mAb-112
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