View source for 5lhr


==The catalytic domain of murine urokinase-type plasminogen activator in complex with the active site binding inhibitory nanobody Nb22==
<StructureSection load='5lhr' size='340' side='right'caption='[[5lhr]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lhr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LHR 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]] 2.3&#8491;</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=5lhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lhr OCA], [https://pdbe.org/5lhr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lhr RCSB], [https://www.ebi.ac.uk/pdbsum/5lhr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lhr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UROK_MOUSE UROK_MOUSE] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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== Publication Abstract from PubMed ==
Although trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules. The structure of unbound muPA revealed an unsuspected non-chymotrypsin-like protease conformation in which two beta-strands in the core of the protease domain undergoes a major antiparallel-to-parallel conformational transition. We next isolated two anti-muPA nanobodies; an active-site binding nanobody and an allosteric nanobody. Crystal structures of the muPA:nanobody complexes and hydrogen-deuterium exchange mass spectrometry revealed molecular insights about molecular factors controlling the antiparallel-to-parallel equilibrium in muPA. Together with muPA activity assays, the data provide valuable insights into regulatory mechanisms and conformational flexibility of uPA and trypsin-like serine proteases in general.

Discovery of a novel conformational equilibrium in urokinase-type plasminogen activator.,Kromann-Hansen T, Louise Lange E, Peter Sorensen H, Hassanzadeh-Ghassabeh G, Huang M, Jensen JK, Muyldermans S, Declerck PJ, Komives EA, Andreasen PA Sci Rep. 2017 Jun 13;7(1):3385. doi: 10.1038/s41598-017-03457-7. PMID:28611361<ref>PMID:28611361</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lhr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Plasminogen activator|Plasminogen activator]]
*[[Urokinase 3D Structures|Urokinase 3D Structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Vicugna pacos]]
[[Category: Andreasen PA]]
[[Category: Declerck PJ]]
[[Category: Ghassabeh GH]]
[[Category: Huang M]]
[[Category: Jensen JK]]
[[Category: Kromann-Hansen T]]
[[Category: Lange EL]]
[[Category: Muyldermans S]]
[[Category: Sorensen HP]]