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| | <StructureSection load='4auo' size='340' side='right'caption='[[4auo]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='4auo' size='340' side='right'caption='[[4auo]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4auo]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AUO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4auo]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AUO FirstGlance]. <br> |
| - | </td></tr><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=ZN:ZINC+ION'>ZN</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]] 3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene></td></tr> | + | <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=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ayk|1ayk]], [[1cge|1cge]], [[1cgf|1cgf]], [[1cgl|1cgl]], [[1hfc|1hfc]], [[1su3|1su3]], [[2ayk|2ayk]], [[2clt|2clt]], [[2j0t|2j0t]], [[2tcl|2tcl]], [[3ayk|3ayk]], [[4ayk|4ayk]], [[966c|966c]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.7 3.4.24.7] </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=4auo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4auo OCA], [https://pdbe.org/4auo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4auo RCSB], [https://www.ebi.ac.uk/pdbsum/4auo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4auo ProSAT]</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=4auo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4auo OCA], [https://pdbe.org/4auo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4auo RCSB], [https://www.ebi.ac.uk/pdbsum/4auo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4auo ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MMP1_HUMAN MMP1_HUMAN]] Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.<ref>PMID:1645757</ref>
| + | [https://www.uniprot.org/uniprot/MMP1_HUMAN MMP1_HUMAN] Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.<ref>PMID:1645757</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Interstitial collagenase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bihan, D]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Carafoli, F]] | + | [[Category: Bihan D]] |
| - | [[Category: Enghild, J J]] | + | [[Category: Carafoli F]] |
| - | [[Category: Farndale, R W]] | + | [[Category: Enghild JJ]] |
| - | [[Category: Hohenester, E]] | + | [[Category: Farndale RW]] |
| - | [[Category: Manka, S W]] | + | [[Category: Hohenester E]] |
| - | [[Category: Murphy, G]] | + | [[Category: Manka SW]] |
| - | [[Category: Nagase, H]] | + | [[Category: Murphy G]] |
| - | [[Category: Raynal, N]] | + | [[Category: Nagase H]] |
| - | [[Category: Visse, R]] | + | [[Category: Raynal N]] |
| - | [[Category: Hydrolase-peptide complex]]
| + | [[Category: Visse R]] |
| Structural highlights
Function
MMP1_HUMAN Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.[1]
Publication Abstract from PubMed
Collagenases of the matrix metalloproteinase (MMP) family play major roles in morphogenesis, tissue repair, and human diseases, but how they recognize and cleave the collagen triple helix is not fully understood. Here, we report temperature-dependent binding of a catalytically inactive MMP-1 mutant (E200A) to collagen through the cooperative action of its catalytic and hemopexin domains. Contact between the two molecules was mapped by screening the Collagen Toolkit peptide library and by hydrogen/deuterium exchange. The crystal structure of MMP-1(E200A) bound to a triple-helical collagen peptide revealed extensive interactions of the 115-A-long triple helix with both MMP-1 domains. An exosite in the hemopexin domain, which binds the leucine 10 residues C-terminal to the scissile bond, is critical for collagenolysis and represents a unique target for inhibitor development. The scissile bond is not correctly positioned for hydrolysis in the crystallized complex. A productive binding mode is readily modeled, without altering the MMP-1 structure or the exosite interactions, by axial rotation of the collagen homotrimer. Interdomain flexing of the enzyme and a localized excursion of the collagen chain closest to the active site, facilitated by thermal loosening of the substrate, may lead to the first transition state of collagenolysis.
Structural insights into triple-helical collagen cleavage by matrix metalloproteinase 1.,Manka SW, Carafoli F, Visse R, Bihan D, Raynal N, Farndale RW, Murphy G, Enghild JJ, Hohenester E, Nagase H Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12461-6. Epub 2012 Jul 3. PMID:22761315[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Desrochers PE, Jeffrey JJ, Weiss SJ. Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity. J Clin Invest. 1991 Jun;87(6):2258-65. PMID:1645757 doi:http://dx.doi.org/10.1172/JCI115262
- ↑ Manka SW, Carafoli F, Visse R, Bihan D, Raynal N, Farndale RW, Murphy G, Enghild JJ, Hohenester E, Nagase H. Structural insights into triple-helical collagen cleavage by matrix metalloproteinase 1. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12461-6. Epub 2012 Jul 3. PMID:22761315 doi:10.1073/pnas.1204991109
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