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| | ==Crystal Structure of the Catalytic Domain of MMP-1 in Complex with the Inhibitory Domain of TIMP-1== | | ==Crystal Structure of the Catalytic Domain of MMP-1 in Complex with the Inhibitory Domain of TIMP-1== |
| - | <StructureSection load='2j0t' size='340' side='right' caption='[[2j0t]], [[Resolution|resolution]] 2.54Å' scene=''> | + | <StructureSection load='2j0t' size='340' side='right'caption='[[2j0t]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2j0t]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J0T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J0T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2j0t]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J0T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2J0T FirstGlance]. <br> |
| - | </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=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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> |
| | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ayk|1ayk]], [[1cge|1cge]], [[1cgf|1cgf]], [[1cgl|1cgl]], [[1hfc|1hfc]], [[1su3|1su3]], [[2ayk|2ayk]], [[2clt|2clt]], [[2tcl|2tcl]], [[3ayk|3ayk]], [[4ayk|4ayk]], [[966c|966c]], [[1d2b|1d2b]], [[1lqn|1lqn]], [[1oo9|1oo9]], [[1uea|1uea]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ayk|1ayk]], [[1cge|1cge]], [[1cgf|1cgf]], [[1cgl|1cgl]], [[1hfc|1hfc]], [[1su3|1su3]], [[2ayk|2ayk]], [[2clt|2clt]], [[2tcl|2tcl]], [[3ayk|3ayk]], [[4ayk|4ayk]], [[966c|966c]], [[1d2b|1d2b]], [[1lqn|1lqn]], [[1oo9|1oo9]], [[1uea|1uea]]</td></tr> |
| | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.7 3.4.24.7] </span></td></tr> | | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j0t OCA], [http://pdbe.org/2j0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j0t RCSB], [http://www.ebi.ac.uk/pdbsum/2j0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j0t ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2j0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j0t OCA], [http://pdbe.org/2j0t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j0t RCSB], [http://www.ebi.ac.uk/pdbsum/2j0t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j0t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
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| | [[Category: Human]] | | [[Category: Human]] |
| | [[Category: Interstitial collagenase]] | | [[Category: Interstitial collagenase]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Acharya, K R]] | | [[Category: Acharya, K R]] |
| | [[Category: Brew, K]] | | [[Category: Brew, K]] |
| Structural highlights
2j0t is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 1ayk, 1cge, 1cgf, 1cgl, 1hfc, 1su3, 2ayk, 2clt, 2tcl, 3ayk, 4ayk, 966c, 1d2b, 1lqn, 1oo9, 1uea |
| Activity: | Interstitial collagenase, with EC number 3.4.24.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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] [TIMP1_HUMAN] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Also mediates erythropoiesis in vitro; but, unlike IL-3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-16. Does not act on MMP-14.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The mammalian collagenases are a subgroup of the matrix metalloproteinases (MMPs) that are uniquely able to cleave triple helical fibrillar collagens. Collagen breakdown is an essential part of extracellular matrix turnover in key physiological processes including morphogenesis and wound healing; however, unregulated collagenolysis is linked to important diseases such as arthritis and cancer. The tissue inhibitors of metalloproteinases (TIMPs) function in controlling the activity of MMPs, including collagenases. We report here the structure of a complex of the catalytic domain of fibroblast collagenase (MMP-1) with the N-terminal inhibitory domain of human TIMP-1 (N-TIMP-1) at 2.54 A resolution. Comparison with the previously reported structure of the TIMP-1/stromelysin-1 (MMP-3) complex shows that the mechanisms of inhibition of both MMPs are generally similar, yet there are significant differences in the protein-protein interfaces in the two complexes. Specifically, the loop between beta-strands A and B of TIMP-1 makes contact with MMP-3 but not with MMP-1, and there are marked differences in the roles of individual residues in the C-D connector of TIMP-1 in binding to the two MMPs. Structural rearrangements in the bound MMPs are also strikingly different. This is the first crystallographic structure that contains the truncated N-terminal domain of a TIMP, which shows only minor differences from the corresponding region of the full-length protein. Differences in the interactions in the two TIMP-1 complexes provide a structural explanation for the results of previous mutational studies and a basis for designing new N-TIMP-1 variants with restricted specificity.
Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1.,Iyer S, Wei S, Brew K, Acharya KR J Biol Chem. 2007 Jan 5;282(1):364-71. Epub 2006 Oct 18. PMID:17050530[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
- ↑ Iyer S, Wei S, Brew K, Acharya KR. Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1. J Biol Chem. 2007 Jan 5;282(1):364-71. Epub 2006 Oct 18. PMID:17050530 doi:10.1074/jbc.M607625200
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