1ck7: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1ck7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CK7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CK7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1ck7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CK7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CK7 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gelatinase_A Gelatinase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.24 3.4.24.24] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gelatinase_A Gelatinase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.24 3.4.24.24] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ck7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ck7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ck7 RCSB], [http://www.ebi.ac.uk/pdbsum/1ck7 PDBsum]</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=1ck7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ck7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ck7 RCSB], [http://www.ebi.ac.uk/pdbsum/1ck7 PDBsum]</span></td></tr>
<table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN]] Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:[http://omim.org/entry/259600 259600]]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.<ref>PMID:11431697</ref> <ref>PMID:15691365</ref> <ref>PMID:16542393</ref>   
[[http://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN]] Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:[http://omim.org/entry/259600 259600]]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.<ref>PMID:11431697</ref> <ref>PMID:15691365</ref> <ref>PMID:16542393</ref>   
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[[Category: Gelatinase A]]
[[Category: Gelatinase A]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bergmann, U.]]
[[Category: Bergmann, U]]
[[Category: Isupov, M.]]
[[Category: Isupov, M]]
[[Category: Lindqvist, Y.]]
[[Category: Lindqvist, Y]]
[[Category: Morgunova, E.]]
[[Category: Morgunova, E]]
[[Category: Schneider, G.]]
[[Category: Schneider, G]]
[[Category: Tryggvason, K.]]
[[Category: Tryggvason, K]]
[[Category: Tuuttila, A.]]
[[Category: Tuuttila, A]]
[[Category: Full-length]]
[[Category: Full-length]]
[[Category: Gelatinase some]]
[[Category: Gelatinase some]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Metalloproteinase]]
[[Category: Metalloproteinase]]

Revision as of 22:33, 22 December 2014

GELATINASE A (FULL-LENGTH)GELATINASE A (FULL-LENGTH)

Structural highlights

1ck7 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Activity:Gelatinase A, with EC number 3.4.24.24
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[MMP2_HUMAN] Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:259600]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.[1] [2] [3]

Function

[MMP2_HUMAN] Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro.[4] [5] [6] [7] [8] [9] [10] PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.[11] [12] [13] [14] [15] [16] [17] Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.[18] [19] [20] [21] [22] [23] [24]

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

Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases characterized by abnormal connective tissue turnover. MMPs are expressed as latent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure of proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of loops essential for propeptide stability.

Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.,Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K Science. 1999 Jun 4;284(5420):1667-70. PMID:10356396[25]

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

See Also

References

  1. ↑ Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ. Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nat Genet. 2001 Jul;28(3):261-5. PMID:11431697 doi:10.1038/90100
  2. ↑ Zankl A, Bonafe L, Calcaterra V, Di Rocco M, Superti-Furga A. Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. Clin Genet. 2005 Mar;67(3):261-6. PMID:15691365 doi:10.1111/j.1399-0004.2004.00402.x
  3. ↑ Rouzier C, Vanatka R, Bannwarth S, Philip N, Coussement A, Paquis-Flucklinger V, Lambert JC. A novel homozygous MMP2 mutation in a family with Winchester syndrome. Clin Genet. 2006 Mar;69(3):271-6. PMID:16542393 doi:CGE584
  4. ↑ Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell. 1998 Feb 6;92(3):391-400. PMID:9476898
  5. ↑ Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999 Nov 12;85(10):906-11. PMID:10559137
  6. ↑ Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res. 2000 Oct 13;87(8):670-6. PMID:11029402
  7. ↑ Bello L, Lucini V, Carrabba G, Giussani C, Machluf M, Pluderi M, Nikas D, Zhang J, Tomei G, Villani RM, Carroll RS, Bikfalvi A, Black PM. Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. Cancer Res. 2001 Dec 15;61(24):8730-6. PMID:11751392
  8. ↑ Chattopadhyay N, Mitra A, Frei E, Chatterjee A. Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol. 2001 Nov;127(11):653-8. PMID:11710594
  9. ↑ Kandasamy AD, Schulz R. Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts. Cardiovasc Res. 2009 Sep 1;83(4):698-706. doi: 10.1093/cvr/cvp175. Epub 2009 Jun , 3. PMID:19493954 doi:10.1093/cvr/cvp175
  10. ↑ Lovett DH, Mahimkar R, Raffai RL, Cape L, Maklashina E, Cecchini G, Karliner JS. A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity. PLoS One. 2012;7(4):e34177. doi: 10.1371/journal.pone.0034177. Epub 2012 Apr 3. PMID:22509276 doi:10.1371/journal.pone.0034177
  11. ↑ Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell. 1998 Feb 6;92(3):391-400. PMID:9476898
  12. ↑ Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999 Nov 12;85(10):906-11. PMID:10559137
  13. ↑ Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res. 2000 Oct 13;87(8):670-6. PMID:11029402
  14. ↑ Bello L, Lucini V, Carrabba G, Giussani C, Machluf M, Pluderi M, Nikas D, Zhang J, Tomei G, Villani RM, Carroll RS, Bikfalvi A, Black PM. Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. Cancer Res. 2001 Dec 15;61(24):8730-6. PMID:11751392
  15. ↑ Chattopadhyay N, Mitra A, Frei E, Chatterjee A. Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol. 2001 Nov;127(11):653-8. PMID:11710594
  16. ↑ Kandasamy AD, Schulz R. Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts. Cardiovasc Res. 2009 Sep 1;83(4):698-706. doi: 10.1093/cvr/cvp175. Epub 2009 Jun , 3. PMID:19493954 doi:10.1093/cvr/cvp175
  17. ↑ Lovett DH, Mahimkar R, Raffai RL, Cape L, Maklashina E, Cecchini G, Karliner JS. A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity. PLoS One. 2012;7(4):e34177. doi: 10.1371/journal.pone.0034177. Epub 2012 Apr 3. PMID:22509276 doi:10.1371/journal.pone.0034177
  18. ↑ Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell. 1998 Feb 6;92(3):391-400. PMID:9476898
  19. ↑ Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999 Nov 12;85(10):906-11. PMID:10559137
  20. ↑ Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res. 2000 Oct 13;87(8):670-6. PMID:11029402
  21. ↑ Bello L, Lucini V, Carrabba G, Giussani C, Machluf M, Pluderi M, Nikas D, Zhang J, Tomei G, Villani RM, Carroll RS, Bikfalvi A, Black PM. Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. Cancer Res. 2001 Dec 15;61(24):8730-6. PMID:11751392
  22. ↑ Chattopadhyay N, Mitra A, Frei E, Chatterjee A. Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol. 2001 Nov;127(11):653-8. PMID:11710594
  23. ↑ Kandasamy AD, Schulz R. Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts. Cardiovasc Res. 2009 Sep 1;83(4):698-706. doi: 10.1093/cvr/cvp175. Epub 2009 Jun , 3. PMID:19493954 doi:10.1093/cvr/cvp175
  24. ↑ Lovett DH, Mahimkar R, Raffai RL, Cape L, Maklashina E, Cecchini G, Karliner JS. A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity. PLoS One. 2012;7(4):e34177. doi: 10.1371/journal.pone.0034177. Epub 2012 Apr 3. PMID:22509276 doi:10.1371/journal.pone.0034177
  25. ↑ Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K. Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. Science. 1999 Jun 4;284(5420):1667-70. PMID:10356396

1ck7, resolution 2.80Å

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