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| <StructureSection load='M1.pdb' size='450' side='right' scene='MT1-MMP-TIMP-1_complex/Cv2/8' caption='Complex of MMP14 (magenta) and TIMP-1 (orange) with Ca+2 (green) and Zn+2 (grey) ions (PDB code [[3ma2]])'> | | <StructureSection load='M1.pdb' size='350' side='right' scene='MT1-MMP-TIMP-1_complex/Cv2/8' caption='Complex of MMP14 (magenta) and TIMP-1 (orange) with Ca+2 (green) and Zn+2 (grey) ions (PDB code [[3ma2]])'> |
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| __TOC__ | | __TOC__ |
| == Function == | | == Function == |
| '''Matrix metalloproteinases''' (MMP) are Zinc-dependent endopeptidases. MMP degrades extracellular matrix proteins. They are inhibited by proteases called tissue inhibitors of metalloproteinase (TIMP). The pro-MMP contains a pro-peptide which must be removed to render the MMP active<ref>PMID:10419448</ref>. See details in<br /> | | '''Matrix metalloproteinases''' (MMP) are Zinc-dependent endopeptidases. MMP degrades extracellular matrix proteins. They are inhibited by proteases called tissue inhibitors of metalloproteinase (TIMP). The pro-MMP contains a pro-peptide which must be removed to render the MMP active<ref>PMID:10419448</ref>. See details in<br /> |
| * [[Matrix Metalloproteinase 12]]<br />
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| * [[Molecular Playground/MMP9]]<br />
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| * [[Molecular Playground/MMP9]]<br />
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| * [[Matrix metalloproteinases]]<br /> | | * [[Matrix metalloproteinases]]<br /> |
| * [[Metalloproteases]]<br /> | | * [[Metalloproteases]]<br /> |
| * [[Atragin]] for MMP adamalysin<br />
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| * [[MT1-MMP-TIMP-1 complex]]<br />. | | * [[MT1-MMP-TIMP-1 complex]]<br />. |
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| MMPs are produced by 28 different genes and are classified according to their protein substrates.<br /> | | MMPs are produced by 28 different genes and are classified according to their protein substrates.<br /> |
| * MMP1 cleaves collagens I, II, III, VII and X.<br /> | | * '''MMP1''' cleaves collagens I, II, III, VII and X.<br /> |
| * MMP2 cleaves collagen IV and denatured collagen.<br /> | | * '''MMP2''' cleaves collagen IV and denatured collagen.<br /> |
| * MMP3 cleaves the core protein of aggrecan and plasminogen activator.<br /> | | * '''MMP3''' cleaves the core protein of aggrecan and plasminogen activator.<br /> |
| * MMP7 cleaves proteoglycans, fibronectin, elastin and casein.<br /> | | * '''MMP7''' cleaves proteoglycans, fibronectin, elastin and casein.<br /> |
| * MMP8 cleaves aggrecan.<br /> | | * '''MMP8''' cleaves aggrecan.<br /> |
| * MMP9 cleaves gelatin. See details in [[Molecular Playground/MMP9]]<br /> | | * '''MMP9''' cleaves gelatin. See details in [[Molecular Playground/MMP9]]<br /> |
| * MMP10 cleaves collagens III, IV, V, fibronectin,gelatin and aggrecan.<br /> | | * '''MMP10''' cleaves collagens III, IV, V, fibronectin,gelatin and aggrecan.<br /> |
| * MMP11 cleaves peptides in human tumors.<br /> | | * '''MMP11''' cleaves peptides in human tumors.<br /> |
| * MMP12 cleaves collagens I and III. See details in [[Matrix Metalloproteinase 12]] <br /> | | * '''MMP12''' cleaves collagens I and III. See details in [[Matrix Metalloproteinase 12]] <br /> |
| * MMP13 cleaves collagen II and laminin-5 γ2.<br /> | | * '''MMP13''' cleaves collagen II and laminin-5 γ2.<br /> |
| * MMP14 is a membrane-type MMP which cleaves aggrecan. See details in [[Molecular Playground/MMP14]]<br /> | | * '''MMP14''' is a membrane-type MMP which cleaves aggrecan. See details in [[Molecular Playground/MMP14]]<br /> |
| | * '''MMP16''' cleaves collagen III, proteoglycans, fibronectin, gelatin, vitronectin, laminin and α2-macroglobulin.<br /> |
| | * '''MMP20''' cleaves E-cadherin.<br /> |
| | * '''MMP23''' function is unknown.<br /> |
| | * '''MMP adamalysin''' is a snake toxin. See details in [[Atragin]]<br /> |
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| == Relevance == | | == Relevance == |
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| account for the entire binding effect between MT1-MMP and TIMP-1. Statistical analysis of the <scene name='MT1-MMP-TIMP-1_complex/Cv2/15'>key hydrogen bond</scene> stabilities in the TIMP-1 T98L mutant reveals that the hydrogen bonds network in mutant form is significantly more stable than that in WT-TIMP-1. Mutations that enhance hydrogen | | account for the entire binding effect between MT1-MMP and TIMP-1. Statistical analysis of the <scene name='MT1-MMP-TIMP-1_complex/Cv2/15'>key hydrogen bond</scene> stabilities in the TIMP-1 T98L mutant reveals that the hydrogen bonds network in mutant form is significantly more stable than that in WT-TIMP-1. Mutations that enhance hydrogen |
| bond stability contribute to the stability of the bound-like, less flexible, conformation of TIMP-1, which eventually results in increasing binding affinity for MT1-MMP. Thus, mutation affected the instrinsic dynamics of the inhibitor rather than its structure, thereby facilitating the interaction <ref name="Grossman">PMID:20545310</ref>. | | bond stability contribute to the stability of the bound-like, less flexible, conformation of TIMP-1, which eventually results in increasing binding affinity for MT1-MMP. Thus, mutation affected the instrinsic dynamics of the inhibitor rather than its structure, thereby facilitating the interaction <ref name="Grossman">PMID:20545310</ref>. |
| </StructureSection>
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| ==3D structures of matrix metalloproteinase== | | ==3D structures of matrix metalloproteinase== |
| | [[Matrix metalloproteinase 3D structures]] |
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
| | </StructureSection> |
| {{#tree:id=OrganizedByTopic|openlevels=0|
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| *MMP1 interstitial or fibroblast collagenase
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| **[[1su3]] – pro-hMMP – human<br />
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| **[[2clt]] – hMMP (mutant)<br />
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| **[[3shi]], [[1hfc]] - hMMP catalytic domain<br />
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| **[[2tcl]], [[966c]] - hMMP catalytic domain + inhibitor<br />
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| **[[2ayk]], [[3ayk]], [[4ayk]] - hMMP catalytic domain - NMR<br />
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| **[[1fbl]] – MMP - pig
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| *MMP2 gelatinase-A
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| **[[1qib]], [[1ck7]] - hMMP catalytic domain (mutant) <BR />
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| **[[1rtg]] - hMMP hemopexin-like domain<BR />
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| **[[1ks0]] – hMMP first fibronectin type II domain – NMR<BR />
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| **[[1cxw]] - hMMP second fibronectin type II domain – NMR<BR />
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| **[[1j7m]] - hMMP third fibronectin type II domain (mutant) – NMR<BR />
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| **[[1gen]] – hMMP C terminal <br />
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| **[[1eak]] – pro-hMMP catalytic domain (mutant) + peptide inhibitor<br />
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| **[[3ayu]] - hMMP catalytic domain (mutant) + peptide inhibitor<br />
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| **[[1hov]], [[1eub]] - hMMP catalytic domain + inhibitor– NMR<BR />
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| **[[1gxd]] – pro-hMMP (mutant) + TIMP-2
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| *MMP3 stromelysin 1
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| **[[1qia]], [[1qic]], [[1cqr]], [[1slm]] - hMMP catalytic domain<BR />
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| **[[3ohl]], [[3oho]], [[1g49]], [[1ciz]], [[1b8y]], [[1caq]], [[1usn]], [[2usn]], [[1ums]], [[1umt]], [[2d1n]], [[2d1o]], [[2ow9]], [[1bqo]], [[1g4k]], [[1b3d]], [[1biw]], [[1c3i]], [[1d5j]], [[1d7x]], [[1d8f]], [[1d8m]], [[1g05]], [[1hfs]], [[1hy7]], [[2srt]], [[4dpe]], [[4g9l]], [[4ja1]] - hMMP catalytic domain + inhibitor<br />
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| **[[1c8t]] - hMMP catalytic domain (mutant) + inhibitor<br />
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| **[[1uea]] - hMMP catalytic domain + TIMP-1<BR />
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| **[[1oo9]] - hMMP catalytic domain + TIMP-1 N terminal<BR />
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| **[[2jt5]], [[2jt6]], [[2jnp]], [[3usn]], [[1sln]], [[1bm6]] - hMMP catalytic domain + inhibitor – NMR<BR />
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| *MMP7 matrilysin
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| **[[2y6c]], [[2y6d]], [[2ddy]], [[1mmp]], [[1mmq]], [[1mmr]] – hMMP catalytic domain + inhibitor<br />
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| *MMP8 neutrophil collagenase
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| **[[2oy4]], [[1mnc]] - hMMP catalytic domain<br />
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| **[[3dng]], [[3dpe]], [[3dpf]], [[1zp5]], [[1jh1]], [[1jj9]], [[1i76]], [[1a85]], [[1mmb]], [[1zs0]], [[1zvx]], [[1lbc]] – hMMP catalytic domain + inhibitor<br />
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| **[[1i73]], [[2oy2]], [[1jan]], [[1jao]], [[1jap]], [[1jaq]] - hMMP catalytic domain + peptide inhibitor<br />
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| **[[1a86]] - hMMP catalytic domain + aspartate-based inhibitor
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| *MMP9 gelatinase-B
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| **[[1l6j]] - pro-hMMP<BR />
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| **[[1itv]] – hMMP haemopexin-like domain<br />
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| **[[1gkc]], [[4xct]] - hMMP catalytic domain + inhibitor<br />
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| **[[2ovx]], [[2ovz]], [[2ow0]], [[2ow1]], [[2ow2]], [[1gkd]], [[4h1q]], [[4h82]], [[4hma]], [[4h2e]], [[4h3x]] - hMMP catalytic domain (mutant) + inhibitor<br />
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| **[[4jij]], [[4jqg]] - hMMP catalytic domain (mutant) + FRET substrate<br />
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| *MMP10 stromelysin 2
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| **[[1q3a]] - hMMP catalytic domain (mutant)<br />
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| **[[3v96]], [[4ilw]] - hMMP catalytic domain + metalloproteinase inhibitor
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| *MMP11 stromelysin 3
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| **[[1hv5]] - hMMP catalytic domain + inhibitor<br />
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| *MMP12 macrophage
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| **[[3ba0]], [[2oxu]] - hMMP<BR />
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| **[[2krj]], [[2k9c]] - hMMP catalytic domain – NMR<BR />
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| **[[1jk3]], [[1jiz]], [[2oxu]] - hMMP catalytic domain <BR />
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| **[[4ijo]] - hMMP catalytic domain (mutant)<br />
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| **[[2poj]] - hMMP catalytic domain (mutant) - NMR<BR />
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| **[[2jxy]] - hMMP hemopexin-like domain - NMR<BR />
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| **[[3n2u]], [[3n2v]], [[2wo8]], [[2wo9]], [[2woa]], [[1utt]], [[1utz]], [[1ros]], [[3rts]], [[3rtt]] – hMMP catalytic domain + inhibitor<br />
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| **[[3lk8]], [[3lik]], [[3lil]], [[3lir]], [[3ljg]], [[3nx7]], [[3lka]], [[3ehx]], [[3ehy]], [[3f15]], [[3f16]], [[3f17]], [[3f18]], [[3f19]], [[3f1a]], [[1y93]], [[1rmz]], [[1os2]], [[1os9]], [[2hu6]], [[3ts4]], [[3tsk]], [[3uvc]], [[4gql]], [[4gr0]], [[4gr3]], [[4gr8]], [[4h30]], [[4h49]], [[4h76]], [[4h84]], [[4io3]], [[1jk3]],[[4efs]], [[4gql]], [[4gr0]], [[4gr3]], [[4gr8]], [[4guy]], [[4h30]], [[4h49]], [[4h76]], [[4h84]], [[4i03]] - hMMP catalytic domain (mutant) + inhibitor<br />
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| **[[2oxn]], [[2oxz]], [[2oxw]] - hMMP catalytic domain (mutant) + peptide<br />
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| **[[2k2g]], [[2z2d]] - hMMP catalytic domain + inhibitor - NMR<BR />
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| **[[2w0d]], [[1ycm]], [[1z3j]] - hMMP catalytic domain (mutant) + inhibitor - NMR<BR />
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| *MMP13 collagenase 3
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| **[[1cxv]] - MMP catalytic domain - mouse<BR />
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| **[[1pex]] – hMMP hemopexin-like domain<br />
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| **[[2yig]], [[3ljz]], [[3kec]], [[3kej]], [[3kek]], [[3kry]], [[3i7g]], [[3i7i]], [[3elm]], [[2pjt]], [[2ozr]], [[1xuc]], [[1xud]], [[1xur]], [[1you]], [[1ztq]], [[3o2x]], [[3zxh]], [[4a7b]], [[1fls]], [[1fm1]], [[456c]], [[830c]], [[3tvc]], [[4jp4]], [[4jpa]] – hMMP catalytic domain + inhibitor<br />
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| **[[2e2d]] - hMMP catalytic domain + TIMP-2<br />
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| **[[4fu4]], [[4fvl]], [[4g0d]] - hMMP catalytic domain (mutant) + pro-domain peptide<br />
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| *MMP14 Membrane T1
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| **[[3ma2]] – hMMP residues 112-292 + TIMP-1 (mutant) <BR />
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| **[[1buv]], [[1bqq]] - hMMP + TIMP-2<BR />
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| **[[3c7x]] – hMMP hemopexin-like domain<br />
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| **[[2mqs]] - hMMP + collagen<br />
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| *MMP16 Membrane T3
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| **[[1rm8]] - hMMP catalytic domain + inhibitor<br />
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| *MMP20 enamelysin
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| **[[2jsd]] - hMMP catalytic domain + inhibitor - NMR<BR />
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| *MMP23 CA-MMP
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| **[[2k72]] – hMMP residues 254-290 - NMR<BR />
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| *MMP adamalysin
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| **[[1iag]] – MMP – diamondback rattlesnake<br />
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| **[[3k7l]] - MMP - cobra<br />
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| }}
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| ==References== | | ==References== |