View source for 4ziq


==Crystal structure of trypsin activated alpha-2-macroglobulin from Escherichia coli.==
<StructureSection load='4ziq' size='340' side='right'caption='[[4ziq]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ziq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZIQ 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]] 2.55&#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=GOL:GLYCEROL'>GOL</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=4ziq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ziq OCA], [https://pdbe.org/4ziq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ziq RCSB], [https://www.ebi.ac.uk/pdbsum/4ziq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ziq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A2MG_ECOLI A2MG_ECOLI] Protects the bacterial cell from host peptidases (PubMed:18697741, PubMed:26143919, PubMed:26100869). Acts by a 'trapping' mechanism. Cleavage of the bait-region domain by host peptidases leads to a global conformational change, which results in entrapment of the host peptidase and activation of the thioester bond that covalently binds the attacking host peptidase (PubMed:26143919, PubMed:26100869). Trapped peptidases are still active except against very large substrates (PubMed:26100869). May protect the entire periplam, including the lipoproteins anchored to the periplasmic side of the outer membrane, against intruding endopeptidases (PubMed:26100869).<ref>PMID:18697741</ref> <ref>PMID:26100869</ref> <ref>PMID:26143919</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The survival of commensal bacteria requires them to evade host peptidases. Gram-negative bacteria from the human gut microbiome encode a relative of the human endopeptidase inhibitor, alpha2-macroglobulin (alpha2M). Escherichia coli alpha2M (ECAM) is a approximately 180-kDa multidomain membrane-anchored pan-peptidase inhibitor, which is cleaved by host endopeptidases in an accessible bait region. Structural studies by electron microscopy and crystallography reveal that this cleavage causes major structural rearrangement of more than half the 13-domain structure from a native to a compact induced form. It also exposes a reactive thioester bond, which covalently traps the peptidase. Subsequently, peptidase-laden ECAM is shed from the membrane and may dimerize. Trapped peptidases are still active except against very large substrates, so inhibition potentially prevents damage of large cell envelope components, but not host digestion. Mechanistically, these results document a novel monomeric "snap trap."

Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition.,Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2015 Jun 22. pii: 201506538. PMID:26100869<ref>PMID:26100869</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ziq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Arede P]]
[[Category: Caston JR]]
[[Category: Duquerroy S]]
[[Category: Garcia-Ferrer I]]
[[Category: Gomez-Blanco J]]
[[Category: Gomis-Ruth XF]]
[[Category: Goulas T]]
[[Category: Luque D]]