2fd6: Difference between revisions

New page: left|200px<br /> <applet load="2fd6" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fd6, resolution 1.90Å" /> '''Structure of Human ...
 
No edit summary
 
(17 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2fd6.gif|left|200px]]<br />
<applet load="2fd6" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2fd6, resolution 1.90&Aring;" />
'''Structure of Human Urokinase Plasminogen Activator in Complex with Urokinase Receptor and an anti-upar antibody at 1.9 A'''<br />


==Overview==
==Structure of Human Urokinase Plasminogen Activator in Complex with Urokinase Receptor and an anti-upar antibody at 1.9 A==
The urokinase plasminogen activator binds to its cellular receptor with, high affinity and initiates signaling cascades that are implicated in, pathological processes including tumor growth, metastasis, and, inflammation. We report the crystal structure at 1.9 angstroms of the, urokinase receptor complexed with the urokinase amino-terminal fragment, and an antibody against the receptor. The three domains of urokinase, receptor form a concave shape with a central cone-shaped cavity where the, urokinase fragment inserts. The structure provides insight into the, flexibility of the urokinase receptor that enables its interaction with a, wide variety of ligands and a basis for the design of urokinase-urokinase, receptor antagonists.
<StructureSection load='2fd6' size='340' side='right'caption='[[2fd6]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2fd6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FD6 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ETX:2-ETHOXYETHANOL'>ETX</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=2fd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fd6 OCA], [https://pdbe.org/2fd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fd6 RCSB], [https://www.ebi.ac.uk/pdbsum/2fd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fd6 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://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 ==
[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
== 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/fd/2fd6_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=2fd6 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation. We report the crystal structure at 1.9 angstroms of the urokinase receptor complexed with the urokinase amino-terminal fragment and an antibody against the receptor. The three domains of urokinase receptor form a concave shape with a central cone-shaped cavity where the urokinase fragment inserts. The structure provides insight into the flexibility of the urokinase receptor that enables its interaction with a wide variety of ligands and a basis for the design of urokinase-urokinase receptor antagonists.


==Disease==
Structure of human urokinase plasminogen activator in complex with its receptor.,Huai Q, Mazar AP, Kuo A, Parry GC, Shaw DE, Callahan J, Li Y, Yuan C, Bian C, Chen L, Furie B, Furie BC, Cines DB, Huang M Science. 2006 Feb 3;311(5761):656-9. PMID:16456079<ref>PMID:16456079</ref>
Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191840 191840]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2FD6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG, SO4, ETX, PG4, EDO and PGE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FD6 OCA].
</div>
<div class="pdbe-citations 2fd6" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure of human urokinase plasminogen activator in complex with its receptor., Huai Q, Mazar AP, Kuo A, Parry GC, Shaw DE, Callahan J, Li Y, Yuan C, Bian C, Chen L, Furie B, Furie BC, Cines DB, Huang M, Science. 2006 Feb 3;311(5761):656-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16456079 16456079]
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Urokinase 3D Structures|Urokinase 3D Structures]]
*[[Urokinase plasminogen activator surface receptor 3D structures|Urokinase plasminogen activator surface receptor 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Huai Q]]
[[Category: U-plasminogen activator]]
[[Category: Huang M]]
[[Category: Huai, Q.]]
[[Category: Li Y]]
[[Category: Huang, M.]]
[[Category: Li, Y.]]
[[Category: EDO]]
[[Category: ETX]]
[[Category: NAG]]
[[Category: PG4]]
[[Category: PGE]]
[[Category: SO4]]
[[Category: atf]]
[[Category: atn-615 antibody]]
[[Category: crystal structure]]
[[Category: fab]]
[[Category: ternary complex]]
[[Category: upar]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:03:34 2007''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA