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| | ==Crystal Structure of Matriptase in complex with Inhibitor".== | | ==Crystal Structure of Matriptase in complex with Inhibitor".== |
| - | <StructureSection load='4jzi' size='340' side='right' caption='[[4jzi]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4jzi' size='340' side='right'caption='[[4jzi]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jzi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JZI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JZI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jzi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JZI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N4C:N-(TRANS-4-AMINOCYCLOHEXYL)-2,6-BIS(4-CARBAMIMIDOYLPHENOXY)PYRIDINE-4-CARBOXAMIDE'>N4C</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jyt|4jyt]], [[4jz1|4jz1]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N4C:N-(TRANS-4-AMINOCYCLOHEXYL)-2,6-BIS(4-CARBAMIMIDOYLPHENOXY)PYRIDINE-4-CARBOXAMIDE'>N4C</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ST14, PRSS14, SNC19, TADG15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4jzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jzi OCA], [https://pdbe.org/4jzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jzi RCSB], [https://www.ebi.ac.uk/pdbsum/4jzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jzi ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Matriptase Matriptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.109 3.4.21.109] </span></td></tr>
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| - | <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=4jzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jzi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jzi RCSB], [http://www.ebi.ac.uk/pdbsum/4jzi PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN]] Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:[http://omim.org/entry/610765 610765]]. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.<ref>PMID:17273967</ref> | + | [https://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN] Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:[https://omim.org/entry/610765 610765]. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.<ref>PMID:17273967</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN]] Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. | + | [https://www.uniprot.org/uniprot/ST14_HUMAN ST14_HUMAN] Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4jzi" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Matriptase|Matriptase]] | + | *[[Matriptase 3D structures|Matriptase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Matriptase]] | + | [[Category: Large Structures]] |
| - | [[Category: Ashok, K N]] | + | [[Category: Ashok KN]] |
| - | [[Category: Chakshusmathi, G]] | + | [[Category: Chakshusmathi G]] |
| - | [[Category: Chandra, R B]] | + | [[Category: Chandra RB]] |
| - | [[Category: Ramesh, K S]] | + | [[Category: Ramesh KS]] |
| - | [[Category: Subramanya, H S]] | + | [[Category: Subramanya HS]] |
| - | [[Category: Complex structure]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Disease
ST14_HUMAN Defects in ST14 are a cause of ichthyosis autosomal recessive with hypotrichosis (ARIH) [MIM:610765. ARIH is a skin disorder characterized by congenital ichthyosis associated with the presence of less than the normal amount of hair.[1]
Function
ST14_HUMAN Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site.
Publication Abstract from PubMed
Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other serine proteases.
Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors.,Goswami R, Mukherjee S, Wohlfahrt G, Ghadiyaram C, Nagaraj J, Chandra BR, Sistla RK, Satyam LK, Samiulla DS, Moilanen A, Subramanya HS, Ramachandra M ACS Med Chem Lett. 2013 Oct 7;4(12):1152-7. doi: 10.1021/ml400213v. eCollection, 2013 Dec 12. PMID:24900621[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Basel-Vanagaite L, Attia R, Ishida-Yamamoto A, Rainshtein L, Ben Amitai D, Lurie R, Pasmanik-Chor M, Indelman M, Zvulunov A, Saban S, Magal N, Sprecher E, Shohat M. Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase. Am J Hum Genet. 2007 Mar;80(3):467-77. Epub 2007 Jan 23. PMID:17273967 doi:S0002-9297(07)60095-0
- ↑ Goswami R, Mukherjee S, Wohlfahrt G, Ghadiyaram C, Nagaraj J, Chandra BR, Sistla RK, Satyam LK, Samiulla DS, Moilanen A, Subramanya HS, Ramachandra M. Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors. ACS Med Chem Lett. 2013 Oct 7;4(12):1152-7. doi: 10.1021/ml400213v. eCollection, 2013 Dec 12. PMID:24900621 doi:http://dx.doi.org/10.1021/ml400213v
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