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4jyt

From Proteopedia

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Crystal Structure of Matriptase in complex with Inhibitor

Structural highlights

4jyt 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.
Method:	X-ray diffraction, Resolution 2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Disease
3 Function
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/4jyt"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4jyt]] 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=4JYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JYT FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N4A:4,4-[{3-[(NAPHTHALEN-2-YLSULFONYL)AMINO]PYRIDINE-2,6-DIYL}BIS(OXY)]DIBENZENECARBOXIMIDAMIDE'>N4A</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]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N4A:4,4-[{3-[(NAPHTHALEN-2-YLSULFONYL)AMINO]PYRIDINE-2,6-DIYL}BIS(OXY)]DIBENZENECARBOXIMIDAMIDE'>N4A</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=4jyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jyt OCA], [https://pdbe.org/4jyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jyt RCSB], [https://www.ebi.ac.uk/pdbsum/4jyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jyt ProSAT]</span></td></tr>
 </table>

4jyt

From Proteopedia

Current revision

Crystal Structure of Matriptase in complex with Inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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