Matriptase: Difference between revisions

Latest revision as of 10:42, 28 October 2019

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Structure of human matriptase catalytic domain complex with benzamidine and sulfate (PDB code 1eax).

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Function

Matriptase or suppressor of tumorigenicity 14 protein (ST14) is an epithelial-derived, membrane multi-domain serine protease. ST14 cleaves and activates hepatocyte growth factor/scatter factor and urokinase plasminogen. Benzamidine is an inhibitor of ST14. ST14 catalytic domain contains residues 615-855^[1].

Relevance

ST14 has a role in ovarian cancer and is a target for anti-cancer therapy^[2]. Inflammation-associated reactive oxygen species and tissue acidity enhance ST14 activation in some skin diseases^[3].

Structural highlights

ST14 active site has the conformation of a typical serine protease like trypsin or chymotrypsin with the Ser-His-Asp catalytic triad and Gly-Ser oxyanion hole. The inhibitor benzamidine blocks the catalytic triad^[4]. Water molecules shown as red spheres.

3D Structures of matriptase

Matriptase 3D structures

↑ List K, Bugge TH, Szabo R. Matriptase: potent proteolysis on the cell surface. Mol Med. 2006 Jan-Mar;12(1-3):1-7. PMID:16838070 doi:https://dx.doi.org/10.2119/2006-00022.List
↑ Johnson MD, Oberst MD, Lin CY, Dickson RB. Possible role of matriptase in the diagnosis of ovarian cancer. Expert Rev Mol Diagn. 2003 May;3(3):331-8. PMID:12779007 doi:https://dx.doi.org/10.1586/14737159.3.3.331
↑ Chen CJ, Wu BY, Tsao PI, Chen CY, Wu MH, Chan YL, Lee HS, Johnson MD, Eckert RL, Chen YW, Chou F, Wang JK, Lin CY. Increased matriptase zymogen activation in inflammatory skin disorders. Am J Physiol Cell Physiol. 2011 Mar;300(3):C406-15. doi:, 10.1152/ajpcell.00403.2010. Epub 2010 Dec 1. PMID:21123732 doi:https://dx.doi.org/10.1152/ajpcell.00403.2010
↑ Friedrich R, Fuentes-Prior P, Ong E, Coombs G, Hunter M, Oehler R, Pierson D, Gonzalez R, Huber R, Bode W, Madison EL. Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase. J Biol Chem. 2002 Jan 18;277(3):2160-8. Epub 2001 Nov 5. PMID:11696548 doi:10.1074/jbc.M109830200

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] List K, Bugge TH, Szabo R. Matriptase: potent proteolysis on the cell surface. Mol Med. 2006 Jan-Mar;12(1-3):1-7. PMID:16838070 doi:https://dx.doi.org/10.2119/2006-00022.List

[2] Johnson MD, Oberst MD, Lin CY, Dickson RB. Possible role of matriptase in the diagnosis of ovarian cancer. Expert Rev Mol Diagn. 2003 May;3(3):331-8. PMID:12779007 doi:https://dx.doi.org/10.1586/14737159.3.3.331

[3] Chen CJ, Wu BY, Tsao PI, Chen CY, Wu MH, Chan YL, Lee HS, Johnson MD, Eckert RL, Chen YW, Chou F, Wang JK, Lin CY. Increased matriptase zymogen activation in inflammatory skin disorders. Am J Physiol Cell Physiol. 2011 Mar;300(3):C406-15. doi:, 10.1152/ajpcell.00403.2010. Epub 2010 Dec 1. PMID:21123732 doi:https://dx.doi.org/10.1152/ajpcell.00403.2010

[4] Friedrich R, Fuentes-Prior P, Ong E, Coombs G, Hunter M, Oehler R, Pierson D, Gonzalez R, Huber R, Bode W, Madison EL. Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase. J Biol Chem. 2002 Jan 18;277(3):2160-8. Epub 2001 Nov 5. PMID:11696548 doi:10.1074/jbc.M109830200

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@@ Line 1: / Line 1: @@
-<StructureSection load='4isn' size='340' side='right' caption='Structure of human matriptase catalytic domain (grey) complex with Kunitz-type protease inhibitor (green) and glutathione (PDB code [[4isn]]). ' scene=''>
+<StructureSection load='1eax' size='350' side='right' caption='Structure of human matriptase catalytic domain complex with benzamidine and sulfate (PDB code [[1eax]]). ' scene='59/595760/Cv/1'>
 == Function ==
-'''Matriptase''' or '''suppressor of tumorigenicity 14 protein''' (ST14) is an epithelial-derived, membrane multi-domain serine protease.  ST14 cleaves and activates hepatocyte frowth factor/scatter factor and urokinase plasminogen.  Benzamidine is an inhibitor of ST14.  ST14 catalytic domain contains residues 615-855.
+'''Matriptase''' or '''suppressor of tumorigenicity 14 protein''' (ST14) is an epithelial-derived, membrane multi-domain serine protease.  ST14 cleaves and activates hepatocyte growth factor/scatter factor and urokinase plasminogen.  Benzamidine is an inhibitor of ST14.  ST14 catalytic domain contains residues 615-855<ref>PMID:16838070</ref>.
-== Disease ==
 == Relevance ==
-ST14 is a target for anti-cancer therapy.
+ST14 has a role in ovarian cancer and is a target for anti-cancer therapy<ref>PMID:12779007</ref>.  Inflammation-associated reactive oxygen species and tissue acidity enhance ST14 activation in some skin diseases<ref>PMID:21123732</ref>.
 == Structural highlights ==
+ST14 active site has the conformation of a typical serine protease like trypsin or chymotrypsin with the <scene name='59/595760/Cv/5'>Ser-His-Asp catalytic triad</scene> and <scene name='59/595760/Cv/6'>Gly-Ser oxyanion hole</scene>.  The <scene name='59/595760/Cv/7'>inhibitor benzamidine blocks the catalytic triad</scene><ref>PMID:11696548</ref>. Water molecules shown as red spheres.
 == 3D Structures of matriptase ==
+[[Matriptase 3D structures]]
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+</StructureSection>
-[[4is5]] – hST14 catalytic domain - human<br />
-===Matriptase complex with small molecule inhibitor===
-[[1eax]] – hST14 catalytic domain + benzamidine <br />
-[[3p8g]] – hST14 residues 182-422 (mutant) + benzamidine <br />
-[[2gv6]] – hST14 catalytic domain + benzamidine derivative<br />
-[[4o97]], [[4o9v]] – hST14 catalytic domain + benzamidine derivative + tetrapeptide<br />
-[[3ncl]] – hST14 catalytic domain (mutant) + benzamidine derivative<br />
-[[2gv7]], [[4jz1]], [[4jzi]], [[4jyt]] – hST14 catalytic domain + inhibitor<br />
-===Matriptase complex with polypeptide inhibitor===
-[[1eaw]] – hST14 catalytic domain + BPTI<br />
-[[3bn9]] – hST14 catalytic domain + antibody<br />
-[[3nps]], [[3so3]] – hST14 catalytic domain (mutant) + antibody<br />
-[[3p8f]] – hST14 residues 182-422 (mutant) + trypsin inhibitor peptide <br />
-[[4isl]], [[4isn]], [[4iso]] – hST14 catalytic domain (mutant) + Kunitz-type protease inhibitor <br />
 == References ==

Matriptase: Difference between revisions

Latest revision as of 10:42, 28 October 2019

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Function

Relevance

Structural highlights

3D Structures of matriptase

References

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