4jz1: Difference between revisions
New page: '''Unreleased structure''' The entry 4jz1 is ON HOLD Authors: Subramanya. H.S, Ravi Chandra. B, Ashok. K.N, Chakshusmathi. G, Ramesh. K.S Description: CRYSTAL STRUCTURE OF MATRIPTASE W... |
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==Crystal Structure of Matriptase in complex with Inhibitor== | |||
<StructureSection load='4jz1' size='340' side='right'caption='[[4jz1]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jz1]] 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=4JZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JZ1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F4D:4,4-[(3-{[(4-FLUOROPHENYL)SULFONYL]AMINO}PYRIDINE-2,6-DIYL)BIS(OXY)]DIBENZENECARBOXIMIDAMIDE'>F4D</scene></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=4jz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jz1 OCA], [https://pdbe.org/4jz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jz1 RCSB], [https://www.ebi.ac.uk/pdbsum/4jz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jz1 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[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 == | |||
[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;"> | |||
== 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<ref>PMID:24900621</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4jz1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Matriptase 3D structures|Matriptase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ashok KN]] | |||
[[Category: Chakshusmathi G]] | |||
[[Category: Ramesh KS]] | |||
[[Category: Ravi BC]] | |||
[[Category: Subramanya HS]] | |||
Latest revision as of 17:26, 8 November 2023
Crystal Structure of Matriptase in complex with InhibitorCrystal Structure of Matriptase in complex with Inhibitor
Structural highlights
DiseaseST14_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] FunctionST14_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 PubMedMatriptase 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 AlsoReferences
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