2mls

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==Membrane Bilayer complex with Matrix Metalloproteinase-12 at its Beta-face==
==Membrane Bilayer complex with Matrix Metalloproteinase-12 at its Beta-face==
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<StructureSection load='2mls' size='340' side='right' caption='[[2mls]], [[NMR_Ensembles_of_Models | 14 NMR models]]' scene=''>
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<StructureSection load='2mls' size='340' side='right'caption='[[2mls]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2mls]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MLS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MLS FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2mls]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MLS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MLS FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2poj|2poj]], [[2mlr|2mlr]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></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=2mls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mls OCA], [https://pdbe.org/2mls PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mls RCSB], [https://www.ebi.ac.uk/pdbsum/2mls PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mls ProSAT]</span></td></tr>
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<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=2mls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mls OCA], [http://pdbe.org/2mls PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mls RCSB], [http://www.ebi.ac.uk/pdbsum/2mls PDBsum]</span></td></tr>
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</table>
</table>
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{{Large structure}}
 
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN]] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
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[https://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Matrix metalloproteinases (MMPs) regulate tissue remodelling, inflammation and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here we demonstrate the binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labelled membrane mimics. Loops project from the beta-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation.
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Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12.,Koppisetti RK, Fulcher YG, Jurkevich A, Prior SH, Xu J, Lenoir M, Overduin M, Van Doren SR Nat Commun. 2014 Nov 21;5:5552. doi: 10.1038/ncomms6552. PMID:25412686<ref>PMID:25412686</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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==See Also==
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</div>
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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<div class="pdbe-citations 2mls" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Macrophage elastase]]
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[[Category: Homo sapiens]]
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[[Category: Doren, S R.Van]]
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[[Category: Large Structures]]
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[[Category: Fulcher, Y G]]
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[[Category: Fulcher YG]]
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[[Category: Koppisetti, R K]]
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[[Category: Koppisetti RK]]
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[[Category: Lenoir, M]]
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[[Category: Lenoir M]]
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[[Category: Overduin, M]]
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[[Category: Overduin M]]
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[[Category: Prior, S H]]
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[[Category: Prior SH]]
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[[Category: Catalytic domain]]
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[[Category: Van Doren SR]]
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[[Category: Hydrolase]]
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[[Category: Membrane-binding of soluble metalloproteinase mmp-12]]
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Current revision

Membrane Bilayer complex with Matrix Metalloproteinase-12 at its Beta-face

PDB ID 2mls

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