4a5t: Difference between revisions

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-'''Unreleased structure'''
-The entry 4a5t is ON HOLD  until sometime in the future
+==STRUCTURAL BASIS FOR THE CONFORMATIONAL MODULATION==
+<StructureSection load='4a5t' size='340' side='right'caption='[[4a5t]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4a5t]] 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=4A5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A5T 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]] 3.49&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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=4a5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5t OCA], [https://pdbe.org/4a5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a5t RCSB], [https://www.ebi.ac.uk/pdbsum/4a5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a5t ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[https://omim.org/entry/217090 217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.<ref>PMID:1986355</ref> <ref>PMID:8392398</ref> <ref>PMID:6216475</ref> <ref>PMID:6238949</ref> <ref>PMID:1427790</ref> <ref>PMID:9242524</ref> <ref>PMID:9858247</ref> <ref>PMID:10233898</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.<ref>PMID:14699093</ref>   Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.<ref>PMID:14699093</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Background: Plasminogen is the zymogen form of plasmin and the precursor of angiostatin, it has been implicated in a variety of disease states including thrombosis, bleeding and cancers. The native plasminogen, known as Glu-plasminogen, contains seven domains comprising the N-terminal peptide domain (NTP), five kringle domains (K1-K5) and the C-terminal serine protease domain (SP). Previous studies have established that the lysine binding site (LBS) of the conserved kringle domains plays a crucial role in mediating the regulation of plasminogen function. However, details of the related conformational mechanism are unknown. Objectives: We aim to understand in more detail the conformational mechanism of plasminogen activation involving the kringles. Methods: We crystallized the native plasminogen under physiologically relevant conditions and determined the structure at 3.5 A resolution. We performed structural analyses and related to the literature data to gain critical understanding of the plasminogen activation. Results and conclusions: The structure reveals the precise architecture of the quaternary complex. It shows that the Glu-plasminogen renders its compact form as an activation-resistant conformation for the proteolytic activation. The LBSs of all kringles, except K1, are engaged in intra-molecular interactions while only K1-LBS is readily available for ligand binding or receptor anchorage. The structure also provides insights into the interactions between plasminogen and alpha2-antiplasmin, the primary physiological inhibitor of plasmin. Furthermore the data represented explains why a conformational transition to the open form is necessary for plasminogen activation as well as angiostatin generation, and provides a rationale for the functional hierarchy of the different kringles. (c) 2012 International Society on Thrombosis and Haemostasis.
-Authors: Xue, Y., Bodin, C., Olsson, K.
+Crystal structure of the native plasminogen reveals an activation-resistant compact conformation.,Xue Y, Bodin C, Olsson K J Thromb Haemost. 2012 Apr 28. doi: 10.1111/j.1538-7836.2012.04765.x. PMID:22540246<ref>PMID:22540246</ref>
-Description: protein
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4a5t" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Plasminogen 3D structures|Plasminogen 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bodin C]]
+[[Category: Olsson K]]
+[[Category: Xue Y]]