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2zec
From Proteopedia
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| - | [[Image:2zec.png|left|200px]] | ||
| - | + | ==Potent, Nonpeptide Inhibitors of Human Mast Cell Tryptase== | |
| + | <StructureSection load='2zec' size='340' side='right'caption='[[2zec]], [[Resolution|resolution]] 2.06Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2zec]] is a 4 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=2ZEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZEC FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=11N:1-[1-(3-PHENYLACRYLOYL)SPIRO[1-BENZOFURAN-3,4-PIPERIDIN]-5-YL]METHANAMINE'>11N</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zeb|2zeb]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPSB2 ([https://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=2zec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zec OCA], [https://pdbe.org/2zec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zec RCSB], [https://www.ebi.ac.uk/pdbsum/2zec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zec ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/TRYB1_HUMAN TRYB1_HUMAN]] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity). | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ze/2zec_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zec ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We have explored a series of spirocyclic piperidine amide derivatives (5) as tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent, selective tryptase inhibitor with oral efficacy in two animal models of airway inflammation (sheep and guinea pig asthma models). An X-ray co-crystal structure of 4 x tryptase revealed a hydrophobic pocket in the enzyme's active site, which is induced by the phenylethynyl group and is comprised of amino acid residues from two different monomers of the tetrameric protein. | ||
| - | + | Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives.,Costanzo MJ, Yabut SC, Zhang HC, White KB, de Garavilla L, Wang Y, Minor LK, Tounge BA, Barnakov AN, Lewandowski F, Milligan C, Spurlino JC, Abraham WM, Boswell-Smith V, Page CP, Maryanoff BE Bioorg Med Chem Lett. 2008 Mar 15;18(6):2114-21. Epub 2008 Jan 30. PMID:18272363<ref>PMID:18272363</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2zec" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[Tryptase|Tryptase]] | *[[Tryptase|Tryptase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: Lewandowski, F | + | [[Category: Human]] |
| - | [[Category: Milligan, C | + | [[Category: Large Structures]] |
| - | [[Category: Spurlino, J C | + | [[Category: Lewandowski, F]] |
| + | [[Category: Milligan, C]] | ||
| + | [[Category: Spurlino, J C]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Serine protease]] | [[Category: Serine protease]] | ||
[[Category: Tryptase]] | [[Category: Tryptase]] | ||
Current revision
Potent, Nonpeptide Inhibitors of Human Mast Cell Tryptase
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