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2bdl
From Proteopedia
(Difference between revisions)
(New page: 200px<br /> <applet load="2bdl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bdl, resolution 2.0Å" /> '''Cathepsin K complexe...) |
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| - | [[Image:2bdl.gif|left|200px]]<br /> | ||
| - | <applet load="2bdl" size="450" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2bdl, resolution 2.0Å" /> | ||
| - | '''Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor'''<br /> | ||
| - | == | + | ==Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor== |
| - | Starting from a potent pantolactone ketoamide cathepsin K inhibitor | + | <StructureSection load='2bdl' size='340' side='right'caption='[[2bdl]], [[Resolution|resolution]] 2.00Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2bdl]] 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=2BDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BDL 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]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PR:(3S)-1-{[(3,5-DIMETHYLISOXAZOL-4-YL)AMINO]CARBONYL}-4,4-DIMETHYLPYRROLIDIN-3-YL{(1S)-1-[1-HYDROXY-2-OXO-2-{[(1R)-1-PHENYLETHYL]AMINO}ETHYL]PENTYL}CARBAMATE'>4PR</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=2bdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bdl OCA], [https://pdbe.org/2bdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bdl RCSB], [https://www.ebi.ac.uk/pdbsum/2bdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bdl ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[https://omim.org/entry/265800 265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.<ref>PMID:8703060</ref> <ref>PMID:9529353</ref> <ref>PMID:10491211</ref> <ref>PMID:10878663</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. | ||
| + | == 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/bd/2bdl_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2bdl ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Starting from a potent pantolactone ketoamide cathepsin K inhibitor discovered from structural screening, conversion of the lactone scaffold to a pyrrolidine scaffold allowed exploration of the S(3) subsite of cathepsin K. Manipulation of P3 and P1' groups afforded potent inhibitors with drug-like properties. | ||
| - | + | Novel, potent P2-P3 pyrrolidine derivatives of ketoamide-based cathepsin K inhibitors.,Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Ray JA, Samano V, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL Bioorg Med Chem Lett. 2006 Mar 15;16(6):1735-9. Epub 2006 Jan 11. PMID:16376075<ref>PMID:16376075</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 2bdl" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | + | *[[Cathepsin 3D structures|Cathepsin 3D structures]] | |
| - | [ | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Shewchuk | + | [[Category: Shewchuk LM]] |
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Current revision
Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor
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