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==Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop Peptide ALP11==
==Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop Peptide ALP11==
<StructureSection load='4dcb' size='340' side='right' caption='[[4dcb]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
<StructureSection load='4dcb' size='340' side='right'caption='[[4dcb]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dcb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dcb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DCB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.033&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pla, YPPCP1.07, YP_pPCP08 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=632 Yersinia pestis])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Plasminogen_activator_Pla Plasminogen activator Pla], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.48 3.4.23.48] </span></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=4dcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcb OCA], [https://pdbe.org/4dcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dcb RCSB], [https://www.ebi.ac.uk/pdbsum/4dcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dcb ProSAT]</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=4dcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dcb RCSB], [http://www.ebi.ac.uk/pdbsum/4dcb PDBsum]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/PLMN_HUMAN PLMN_HUMAN]] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:[http://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 ==
== Function ==
[[http://www.uniprot.org/uniprot/COLY_YERPE COLY_YERPE]] Seems to play an essential role in plague transmission by mediating flea blockage in a temperature-dependent fashion. Fibrinolytic activity prevails at 37 degrees Celsius whereas coagulase expression predominates at lower temperatures (<30 degrees Celsius). Activates plasminogen by cleaving it. [[http://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>
[https://www.uniprot.org/uniprot/PLA_YERPE PLA_YERPE] In the mammalian host activates (cleaves) plasminogen to generate the serine protease plasmin. Plasmin degrades fibrin clots (fibrinolysis) and facilitates bacterial cell migration, enabling rapid dissemination of bacteria from the initial site of infection (Probable). Cleaves host plasminogen to generate plasmin and probably also has autocatalytic activity (PubMed:20637417, PubMed:22645135). Fibrinolytic activity prevails at 37 degrees Celsius whereas coagulase expression predominates at lower temperatures (28 degrees Celsius) (PubMed:2526282). Cleaves plasminogen; plasminogen cleavage is much higher than coagulase activity (PubMed:20637417, PubMed:22645135, PubMed:2526282, PubMed:2651310).<ref>PMID:20637417</ref> <ref>PMID:22645135</ref> <ref>PMID:2526282</ref> <ref>PMID:2651310</ref> <ref>PMID:17635705</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 4dcb" style="background-color:#fffaf0;"></div>
==See Also==
*[[Plasminogen activator|Plasminogen activator]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Plasminogen activator Pla]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Yersinia pestis]]
[[Category: Yersinia pestis]]
[[Category: Berg, B van den]]
[[Category: Eren E]]
[[Category: Eren, E]]
[[Category: Van den Berg B]]
[[Category: Beta barrel]]
[[Category: Hydrolase]]
[[Category: Outer membrane]]
[[Category: Plasminogen activator]]
[[Category: Protease]]

Latest revision as of 09:53, 27 November 2024

Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop Peptide ALP11Y. pestis Plasminogen Activator Pla in Complex with Human Plasminogen Activation Loop Peptide ALP11

Structural highlights

4dcb is a 2 chain structure with sequence from Homo sapiens and Yersinia pestis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.033Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLA_YERPE In the mammalian host activates (cleaves) plasminogen to generate the serine protease plasmin. Plasmin degrades fibrin clots (fibrinolysis) and facilitates bacterial cell migration, enabling rapid dissemination of bacteria from the initial site of infection (Probable). Cleaves host plasminogen to generate plasmin and probably also has autocatalytic activity (PubMed:20637417, PubMed:22645135). Fibrinolytic activity prevails at 37 degrees Celsius whereas coagulase expression predominates at lower temperatures (28 degrees Celsius) (PubMed:2526282). Cleaves plasminogen; plasminogen cleavage is much higher than coagulase activity (PubMed:20637417, PubMed:22645135, PubMed:2526282, PubMed:2651310).[1] [2] [3] [4] [5]

Publication Abstract from PubMed

Omptins constitute a unique family of outer membrane proteases that are widespread in Enterobacteriaceae. The plasminogen activator (Pla) of Yersinia pestis is an omptin family member that is very important for development of both bubonic and pneumonic plague. The physiological function of Pla is to cleave (activate) human plasminogen to form the plasma protease plasmin. Uniquely, lipopolysaccharide (LPS) is essential for the catalytic activity of all omptins, including Pla. Why omptins require LPS for enzymatic activity is unknown. Here, we report the co-crystal structure of LPS-free Pla in complex with the activation loop peptide of human plasminogen, its natural substrate. The structure shows that in the absence of LPS, the peptide substrate binds deep within the active site groove and displaces the nucleophilic water molecule, providing an explanation for the dependence of omptins on LPS for enzymatic activity.

Structural basis for activation of an integral membrane protease by lipopolysaccharide.,Eren E, van den Berg B J Biol Chem. 2012 Jul 6;287(28):23971-6. Epub 2012 May 29. PMID:22645135[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Eren E, Murphy M, Goguen J, van den Berg B. An active site water network in the plasminogen activator pla from Yersinia pestis. Structure. 2010 Jul 14;18(7):809-18. PMID:20637417 doi:10.1016/j.str.2010.03.013
  2. ↑ Eren E, van den Berg B. Structural basis for activation of an integral membrane protease by lipopolysaccharide. J Biol Chem. 2012 Jul 6;287(28):23971-6. Epub 2012 May 29. PMID:22645135 doi:10.1074/jbc.M112.376418
  3. ↑ McDonough KA, Falkow S. A Yersinia pestis-specific DNA fragment encodes temperature-dependent coagulase and fibrinolysin-associated phenotypes. Mol Microbiol. 1989 Jun;3(6):767-75. PMID:2526282 doi:10.1111/j.1365-2958.1989.tb00225.x
  4. ↑ Sodeinde OA, Goguen JD. Nucleotide sequence of the plasminogen activator gene of Yersinia pestis: relationship to ompT of Escherichia coli and gene E of Salmonella typhimurium. Infect Immun. 1989 May;57(5):1517-23. PMID:2651310 doi:10.1128/iai.57.5.1517-1523.1989
  5. ↑ Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost. 2007 Jul;5 Suppl 1:24-31. PMID:17635705 doi:10.1111/j.1538-7836.2007.02519.x
  6. ↑ Eren E, van den Berg B. Structural basis for activation of an integral membrane protease by lipopolysaccharide. J Biol Chem. 2012 Jul 6;287(28):23971-6. Epub 2012 May 29. PMID:22645135 doi:10.1074/jbc.M112.376418

4dcb, resolution 2.03Å

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