3kmc

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<StructureSection load='3kmc' size='340' side='right'caption='[[3kmc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='3kmc' size='340' side='right'caption='[[3kmc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3kmc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KMC FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3kmc]] is a 2 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=3KMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KMC FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=403:(2R,3R)-4-[4-(2-CHLOROPHENYL)PIPERAZIN-1-YL]-2,3-DIHYDROXY-4-OXO-N-(2-THIOPHEN-2-YLETHYL)BUTANAMIDE'>403</scene>, <scene name='pdbligand=INN:N-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE'>INN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bkc|1bkc]], [[3ewj|3ewj]], [[2fv9|2fv9]], [[3kme|3kme]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=403:(2R,3R)-4-[4-(2-CHLOROPHENYL)PIPERAZIN-1-YL]-2,3-DIHYDROXY-4-OXO-N-(2-THIOPHEN-2-YLETHYL)BUTANAMIDE'>403</scene>, <scene name='pdbligand=INN:N-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE'>INN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAM17, CSVP, TACE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/ADAM_17_endopeptidase ADAM 17 endopeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.86 3.4.24.86] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmc OCA], [https://pdbe.org/3kmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kmc RCSB], [https://www.ebi.ac.uk/pdbsum/3kmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kmc ProSAT]</span></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=3kmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmc OCA], [https://pdbe.org/3kmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kmc RCSB], [https://www.ebi.ac.uk/pdbsum/3kmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kmc ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN]] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:[https://omim.org/entry/614328 614328]]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.<ref>PMID:22010916</ref>
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[https://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:[https://omim.org/entry/614328 614328]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.<ref>PMID:22010916</ref>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN]] Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity).<ref>PMID:12441351</ref> <ref>PMID:20592283</ref>
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[https://www.uniprot.org/uniprot/ADA17_HUMAN ADA17_HUMAN] Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity).<ref>PMID:12441351</ref> <ref>PMID:20592283</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: ADAM 17 endopeptidase]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Orth, P]]
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[[Category: Orth P]]
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[[Category: A disintegrin and metalloproteinase domain 17]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Membrane]]
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[[Category: Metal-binding]]
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[[Category: Metalloprotease]]
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[[Category: Notch signaling pathway]]
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[[Category: Phosphoprotein]]
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[[Category: Protease]]
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[[Category: Snake venom-like protease]]
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[[Category: Tnf-alpha convertase]]
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[[Category: Tnf-alpha-converting enzyme]]
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[[Category: Zymogen]]
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Revision as of 08:18, 6 September 2023

Crystal structure of catalytic domain of TACE with tartrate-based inhibitor

PDB ID 3kmc

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