5hpg

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{{Seed}}
 
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[[Image:5hpg.png|left|200px]]
 
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==STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN==
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The line below this paragraph, containing "STRUCTURE_5hpg", creates the "Structure Box" on the page.
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<StructureSection load='5hpg' size='340' side='right'caption='[[5hpg]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[5hpg]] is a 2 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=5HPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HPG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.66&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hpg OCA], [https://pdbe.org/5hpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hpg RCSB], [https://www.ebi.ac.uk/pdbsum/5hpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hpg ProSAT]</span></td></tr>
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{{STRUCTURE_5hpg| PDB=5hpg | SCENE= }}
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hp/5hpg_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=5hpg ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The X-ray crystal structure of the recombinant (r) kringle 5 domain of human plasminogen (K5HPg) has been solved by molecular replacement methods using K1HPg as a model and refined at 1.7 A resolution to an R factor of 16.6%. The asymmetric unit of K5HPg is composed of two molecules related by a noncrystallographic 2-fold rotation axis approximately parallel to the z-direction. The lysine binding site (LBS) is defined by the regions His33-Thr37, Pro54-Val58, Pro61-Tyr64, and Leu71-Tyr74 and is occupied in the apo-form by water molecules. A unique feature of the LBS of apo-K5HPg is the substitution by Leu71 for the basic amino acid, arginine, that in other kringle polypeptides forms the donor cationic center for the carboxylate group of omega-amino acid ligands. While wild-type (wt) r-K5HPg interacted weakly with these types of ligands, replacement by site-directed mutagenesis of Leu71 by arginine led to substantially increased affinity of the ligands for the LBS of K5HPg. As a result, binding of omega-amino acids to this mutant kringle (r-K5HPg[L71R]) was restored to levels displayed by the companion much stronger affinity HPg kringles, K1HPg and K4HPg. Correspondingly, alkylamine binding to r-K5HPg[L71R] was considerably attenuated from that shown by wtr-K5HPg. Thus, employing a rational design strategy based on the crystal structure of K5HPg, successful remodeling of the LBS has been accomplished, and has resulted in the conversion of a weak ligand binding kringle to one that possesses an affinity for omega-amino acids that is similar to K1HPg and K4HPg.
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===STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN===
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Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen.,Chang Y, Mochalkin I, McCance SG, Cheng B, Tulinsky A, Castellino FJ Biochemistry. 1998 Mar 10;37(10):3258-71. PMID:9521645<ref>PMID:9521645</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5hpg" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_9521645}}, adds the Publication Abstract to the page
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*[[Plasminogen 3D structures|Plasminogen 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 9521645 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_9521645}}
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__TOC__
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</StructureSection>
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==About this Structure==
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5HPG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HPG OCA].
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==Reference==
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Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen., Chang Y, Mochalkin I, McCance SG, Cheng B, Tulinsky A, Castellino FJ, Biochemistry. 1998 Mar 10;37(10):3258-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9521645 9521645]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Plasmin]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Castellino FJ]]
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[[Category: Castellino, F J.]]
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[[Category: Mochalkin I]]
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[[Category: Mochalkin, I.]]
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[[Category: Tulinsky A]]
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[[Category: Tulinsky, A.]]
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[[Category: Fibrinolysis]]
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[[Category: Human plasminogen]]
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[[Category: Kringle 5]]
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[[Category: Serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 14:04:32 2008''
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Current revision

STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN

PDB ID 5hpg

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