View source for 4gwm


==Crystal structure of human promeprin beta==
<StructureSection load='4gwm' size='340' side='right'caption='[[4gwm]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gwm]] 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=4GWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GWM 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4gwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwm OCA], [https://pdbe.org/4gwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gwm RCSB], [https://www.ebi.ac.uk/pdbsum/4gwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MEP1B_HUMAN MEP1B_HUMAN] Membrane metallopeptidase that sheds many membrane-bound proteins. Known substrates include: FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C. The presence of several pro-inflammatory cytokine among substrates implicate MEP1B in inflammation. It is also involved in tissue remodeling due to its capability to degrade extracellular matrix components.<ref>PMID:21693781</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Human meprin beta is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid precursor protein (APP) at the beta-secretase site, giving rise to amyloidogenic peptides. We have solved the X-ray crystal structure of a major fragment of the meprin beta ectoprotein, the first of a multidomain oligomeric transmembrane sheddase, and of its zymogen. The meprin beta dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace.

Structural basis for the sheddase function of human meprin beta metalloproteinase at the plasma membrane.,Arolas JL, Broder C, Jefferson T, Guevara T, Sterchi EE, Bode W, Stocker W, Becker-Pauly C, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16131-6. doi:, 10.1073/pnas.1211076109. Epub 2012 Sep 17. PMID:22988105<ref>PMID:22988105</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gwm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arolas JL]]
[[Category: Becker-Pauly C]]
[[Category: Bode W]]
[[Category: Broder C]]
[[Category: Gomis-Ruth FX]]
[[Category: Guevara T]]
[[Category: Jefferson T]]
[[Category: Sterchi EE]]
[[Category: Stocker W]]