Proteopedia

Matrix metalloproteinase: Difference between revisions

← Older edit
Michal Harel (talk | contribs)
31,761 edits
No edit summary
Michal Harel (talk | contribs)
31,761 edits
No edit summary
 
(7 intermediate revisions by the same user not shown)
Line 1: Line 1:
<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]])'>
[[Image:3ma2a.png|left|300px|thumb|MT1-MMP-TIMP-1 complex]]
 
{{Clear}}
__TOC__
'''Matrix metalloproteinases''' (MMP) are Zinc-dependent endopeptidases.  MMP degrades extracellular matrix proteins.  MMPs are produced by 28 different genes and are classified according to their protein substrates.  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. See details in<br />
== Function ==
* [[Matrix Metalloproteinase 12]]<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 />
* [[Molecular Playground/MMP9]]<br />
 
* [[Molecular Playground/MMP14]]<br />
* [[Matrix metalloproteinases]]<br />  
* [[Matrix metalloproteinases]]<br />  
* [[Metalloproteases]]<br />  
* [[Metalloproteases]]<br />  
* [[Atragin]] for MMP adamalysin<br />
* [[MT1-MMP-TIMP-1 complex]]<br />.
* [[MT1-MMP-TIMP-1 complex]]<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 />
* '''MMP2''' cleaves collagen IV and denatured collagen.<br />
* '''MMP3''' cleaves the core protein of aggrecan and plasminogen activator.<br />
* '''MMP7''' cleaves proteoglycans, fibronectin, elastin and casein.<br />
* '''MMP8''' cleaves aggrecan.<br />
* '''MMP9''' cleaves gelatin.  See details in [[Molecular Playground/MMP9]]<br />
* '''MMP10''' cleaves collagens III, IV, V, fibronectin,gelatin and aggrecan.<br />
* '''MMP11''' cleaves peptides in human tumors.<br />
* '''MMP12''' cleaves collagens I and III. See details in [[Matrix Metalloproteinase 12]] <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 />
* '''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 />
== Relevance ==
MMPs have a role in cancer progression<ref>PMID:21087457</ref>.  MMP-2 and MMP-9 secretion is elevated in ovarian cancer and are associated with poor prognosis<ref>PMID:19360311</ref>.  MMP-8, MMP-9, MMP-13 and MMP-14 have a role in periodontal diseases<ref>PMID:8315570</ref>.


{{Clear}}   
{{Clear}}   
Line 19: Line 37:
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>


==3D structures of matrix metalloproteinase==
==3D structures of matrix metalloproteinase==
[[Matrix metalloproteinase 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*MMP1 interstitial or fibroblast collagenase
 
**[[1su3]] – pro-hMMP – human<br />
**[[2clt]] – hMMP (mutant)<br />
**[[3shi]], [[1hfc]] - hMMP catalytic domain<br />
**[[2tcl]], [[966c]] - hMMP catalytic domain + inhibitor<br />
**[[2ayk]], [[3ayk]], [[4ayk]] - hMMP catalytic domain - NMR<br />
**[[1fbl]] – MMP - pig
 
*MMP2 gelatinase-A
 
**[[1qib]], [[1ck7]] - hMMP catalytic domain (mutant) <BR />
**[[1rtg]] - hMMP hemopexin-like domain<BR />
**[[1ks0]] – hMMP first fibronectin type II domain – NMR<BR />
**[[1cxw]] - hMMP second fibronectin type II domain – NMR<BR />
**[[1j7m]] - hMMP third fibronectin type II domain (mutant) – NMR<BR />
**[[1gen]] – hMMP C terminal <br />
**[[1eak]] – pro-hMMP catalytic domain (mutant) + peptide inhibitor<br />
**[[3ayu]] - hMMP catalytic domain (mutant) + peptide inhibitor<br />
**[[1hov]], [[1eub]] - hMMP catalytic domain + inhibitor– NMR<BR />
**[[1gxd]] – pro-hMMP (mutant) + TIMP-2
 
*MMP3 stromelysin 1
 
**[[1qia]], [[1qic]], [[1cqr]], [[1slm]] - hMMP catalytic domain<BR />
**[[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 />
**[[1c8t]] - hMMP catalytic domain (mutant) + inhibitor<br />
**[[1uea]] - hMMP catalytic domain + TIMP-1<BR />
**[[1oo9]] - hMMP catalytic domain + TIMP-1 N terminal<BR />
**[[2jt5]], [[2jt6]], [[2jnp]], [[3usn]], [[1sln]], [[1bm6]] - hMMP catalytic domain + inhibitor – NMR<BR />
 
*MMP7 matrilysin
 
**[[2y6c]], [[2y6d]], [[2ddy]], [[1mmp]], [[1mmq]], [[1mmr]] – hMMP catalytic domain + inhibitor<br />
 
*MMP8 neutrophil collagenase
 
**[[2oy4]], [[1mnc]] - hMMP catalytic domain<br />
**[[3dng]], [[3dpe]], [[3dpf]], [[1zp5]], [[1jh1]], [[1jj9]], [[1i76]], [[1a85]], [[1mmb]], [[1zs0]], [[1zvx]], [[1lbc]] – hMMP catalytic domain + inhibitor<br />
**[[1i73]], [[2oy2]], [[1jan]], [[1jao]], [[1jap]], [[1jaq]] - hMMP catalytic domain + peptide inhibitor<br />
**[[1a86]] - hMMP catalytic domain + aspartate-based inhibitor
 
*MMP9 gelatinase-B
 
**[[1l6j]] - pro-hMMP<BR />
**[[1itv]] – hMMP haemopexin-like domain<br />
**[[1gkc]], [[4xct]] - hMMP catalytic domain + inhibitor<br />
**[[2ovx]], [[2ovz]], [[2ow0]], [[2ow1]], [[2ow2]], [[1gkd]], [[4h1q]], [[4h82]], [[4hma]], [[4h2e]], [[4h3x]] - hMMP catalytic domain (mutant) + inhibitor<br />
**[[4jij]], [[4jqg]] - hMMP catalytic domain (mutant) + FRET substrate<br />
 
*MMP10 stromelysin 2
 
**[[1q3a]] - hMMP catalytic domain (mutant)<br />
**[[3v96]], [[4ilw]] - hMMP catalytic domain + metalloproteinase inhibitor
 
*MMP11 stromelysin 3
 
**[[1hv5]] - hMMP catalytic domain + inhibitor<br />
 
*MMP12 macrophage
 
**[[3ba0]], [[2oxu]] - hMMP<BR />
**[[2krj]], [[2k9c]] - hMMP catalytic domain – NMR<BR />
**[[1jk3]], [[1jiz]], [[2oxu]] -  hMMP catalytic domain <BR />
**[[4ijo]] - hMMP catalytic domain (mutant)<br />
**[[2poj]] - hMMP catalytic domain (mutant) - NMR<BR />
**[[2jxy]] - hMMP hemopexin-like domain - NMR<BR />
**[[3n2u]], [[3n2v]], [[2wo8]], [[2wo9]], [[2woa]], [[1utt]], [[1utz]], [[1ros]], [[3rts]], [[3rtt]] – hMMP catalytic domain + inhibitor<br />
**[[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 />
**[[2oxn]], [[2oxz]], [[2oxw]] - hMMP catalytic domain (mutant) + peptide<br />
**[[2k2g]], [[2z2d]] - hMMP catalytic domain + inhibitor - NMR<BR />
**[[2w0d]], [[1ycm]], [[1z3j]] - hMMP catalytic domain (mutant) + inhibitor - NMR<BR />
 
*MMP13 collagenase 3
 
**[[1cxv]] - MMP catalytic domain - mouse<BR />
**[[1pex]] – hMMP hemopexin-like domain<br />
**[[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 />
**[[2e2d]] - hMMP catalytic domain + TIMP-2<br />
**[[4fu4]], [[4fvl]], [[4g0d]] - hMMP catalytic domain (mutant) + pro-domain peptide<br />
 
*MMP14 Membrane T1
 
**[[3ma2]] – hMMP residues 112-292 + TIMP-1 (mutant) <BR />
**[[1buv]], [[1bqq]] - hMMP + TIMP-2<BR />
**[[3c7x]] – hMMP hemopexin-like domain<br />
**[[2mqs]] - hMMP + collagen<br />
 
*MMP16 Membrane T3
 
**[[1rm8]] - hMMP catalytic domain + inhibitor<br />
 
*MMP20 enamelysin
 
**[[2jsd]] - hMMP catalytic domain + inhibitor - NMR<BR />
 
*MMP23 CA-MMP
 
**[[2k72]] – hMMP residues 254-290 - NMR<BR />
 
*MMP adamalysin
 
**[[1iag]] – MMP – diamondback rattlesnake<br />
**[[3k7l]] - MMP - cobra<br />
}}


==References==
==References==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky
Retrieved from "https://proteopedia.openfox.io/w/Matrix_metalloproteinase"