This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1bqq

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 10:41, 19 May 2021

CRYSTAL STRUCTURE OF THE MT1-MMP--TIMP-2 COMPLEX

Structural highlights

1bqq is a 2 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MMP14_HUMAN] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.^[1] ^[2] [TIMP2_BOVIN] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.

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 proteolytic activity of matrix metalloproteinases (MMPs) towards extracellular matrix components is held in check by the tissue inhibitors of metalloproteinases (TIMPs). The binary complex of TIMP-2 and membrane-type-1 MMP (MT1-MMP) forms a cell surface located 'receptor' involved in pro-MMP-2 activation. We have solved the 2.75 A crystal structure of the complex between the catalytic domain of human MT1-MMP (cdMT1-MMP) and bovine TIMP-2. In comparison with our previously determined MMP-3-TIMP-1 complex, both proteins are considerably tilted to one another and show new features. CdMT1-MMP, apart from exhibiting the classical MMP fold, displays two large insertions remote from the active-site cleft that might be important for interaction with macromolecular substrates. The TIMP-2 polypeptide chain, as in TIMP-1, folds into a continuous wedge; the A-B edge loop is much more elongated and tilted, however, wrapping around the S-loop and the beta-sheet rim of the MT1-MMP. In addition, both C-terminal edge loops make more interactions with the target enzyme. The C-terminal acidic tail of TIMP-2 is disordered but might adopt a defined structure upon binding to pro-MMP-2; the Ser2 side-chain of TIMP-2 extends into the voluminous S1' specificity pocket of cdMT1-MMP, with its Ogamma pointing towards the carboxylate of the catalytic Glu240. The lower affinity of TIMP-1 for MT1-MMP compared with TIMP-2 might be explained by a reduced number of favourable interactions.

Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor.,Fernandez-Catalan C, Bode W, Huber R, Turk D, Calvete JJ, Lichte A, Tschesche H, Maskos K EMBO J. 1998 Sep 1;17(17):5238-48. PMID:9724659^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Golubkov VS, Chekanov AV, Cieplak P, Aleshin AE, Chernov AV, Zhu W, Radichev IA, Zhang D, Dong PD, Strongin AY. The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J Biol Chem. 2010 Nov 12;285(46):35740-9. doi: 10.1074/jbc.M110.165159. Epub 2010, Sep 13. PMID:20837484 doi:http://dx.doi.org/10.1074/jbc.M110.165159
↑ Gu G, Zhao D, Yin Z, Liu P. BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J Cell Biochem. 2012 Mar;113(3):1013-21. doi: 10.1002/jcb.23433. PMID:22065321 doi:10.1002/jcb.23433
↑ Fernandez-Catalan C, Bode W, Huber R, Turk D, Calvete JJ, Lichte A, Tschesche H, Maskos K. Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor. EMBO J. 1998 Sep 1;17(17):5238-48. PMID:9724659 doi:10.1093/emboj/17.17.5238

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bqq"

@@ Line 3: / Line 3: @@
 <StructureSection load='1bqq' size='340' side='right'caption='[[1bqq]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bqq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BQQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BQQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bqq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BQQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BQQ 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='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=1bqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bqq OCA], [http://pdbe.org/1bqq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bqq RCSB], [http://www.ebi.ac.uk/pdbsum/1bqq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1bqq 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=1bqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bqq OCA], [https://pdbe.org/1bqq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bqq RCSB], [https://www.ebi.ac.uk/pdbsum/1bqq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bqq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MMP14_HUMAN MMP14_HUMAN]] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.<ref>PMID:20837484</ref> <ref>PMID:22065321</ref>  [[http://www.uniprot.org/uniprot/TIMP2_BOVIN TIMP2_BOVIN]] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.
+[[https://www.uniprot.org/uniprot/MMP14_HUMAN MMP14_HUMAN]] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.<ref>PMID:20837484</ref> <ref>PMID:22065321</ref>  [[https://www.uniprot.org/uniprot/TIMP2_BOVIN TIMP2_BOVIN]] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 30: @@
 ==See Also==
-*[[MT1-MMP-TIMP-1 complex|MT1-MMP-TIMP-1 complex]]
 *[[Matrix metalloproteinase|Matrix metalloproteinase]]
+*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
 == References ==
 <references/>

1bqq

From Proteopedia

Revision as of 10:41, 19 May 2021

CRYSTAL STRUCTURE OF THE MT1-MMP--TIMP-2 COMPLEX

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox