4wki
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human ADAMTS-4 in complex with inhibitor 5-CHLORO-N-{[(4S)-4-(1-METHYL-1H-IMIDAZOL-2-YL)-2,5-DIOXOIMIDAZOLIDIN-4-YL]METHYL}-1-BENZOFURAN-2-CARBOXAMIDE (compound 11)== | |
| + | <StructureSection load='4wki' size='340' side='right'caption='[[4wki]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4wki]] 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=4WKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WKI 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]] 1.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PW:5-CHLORO-N-{[(4S)-4-(1-METHYL-1H-IMIDAZOL-2-YL)-2,5-DIOXOIMIDAZOLIDIN-4-YL]METHYL}-1-BENZOFURAN-2-CARBOXAMIDE'>3PW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4wki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wki OCA], [https://pdbe.org/4wki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wki RCSB], [https://www.ebi.ac.uk/pdbsum/4wki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wki ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ATS4_HUMAN ATS4_HUMAN] Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 are zinc metalloproteases commonly referred to as aggrecanase-1 and aggrecanase-2, respectively. These enzymes are involved in the degradation of aggrecan, a key component of cartilage. Inhibitors of these enzymes could be potential osteoarthritis (OA) therapies. A series of hydantoin inhibitors of ADAMTS-4 and ADAMTS-5 were identified from a screening campaign and optimized through structure-based drug design to give hydantoin 13. Hydantoin 13 had excellent selectivity over other zinc metalloproteases such as TACE, MMP2, MMP3, MMP13, and MMP14. The compound also produced efficacy in both a chemically induced and surgical model of OA in rats. | ||
| - | + | Identification of Potent and Selective Hydantoin Inhibitors of Aggrecanase-1 and Aggrecanase-2 That Are Efficacious in Both Chemical and Surgical Models of Osteoarthritis.,Durham TB, Klimkowski VJ, Rito CJ, Marimuthu J, Toth JL, Liu C, Durbin JD, Stout SL, Adams L, Swearingen C, Lin C, Chambers MG, Thirunavukkarasu K, Wiley MR J Med Chem. 2014 Dec 5. PMID:25415648<ref>PMID:25415648</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4wki" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[A Disintegrin And Metalloproteinase 3D structures|A Disintegrin And Metalloproteinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Durbin JD]] | ||
Current revision
Crystal structure of human ADAMTS-4 in complex with inhibitor 5-CHLORO-N-{[(4S)-4-(1-METHYL-1H-IMIDAZOL-2-YL)-2,5-DIOXOIMIDAZOLIDIN-4-YL]METHYL}-1-BENZOFURAN-2-CARBOXAMIDE (compound 11)
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