1tu6: Difference between revisions
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==Cathepsin K complexed with a ketoamide inhibitor== | ==Cathepsin K complexed with a ketoamide inhibitor== | ||
<StructureSection load='1tu6' size='340' side='right' caption='[[1tu6]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='1tu6' size='340' side='right'caption='[[1tu6]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1tu6]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1tu6]] 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=1TU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TU6 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSP:[1-(4-FLUOROBENZYL)CYCLOBUTYL]METHYL+(1S)-1-[OXO(1H-PYRAZOL-5-YLAMINO)ACETYL]PENTYLCARBAMATE'>FSP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSP:[1-(4-FLUOROBENZYL)CYCLOBUTYL]METHYL+(1S)-1-[OXO(1H-PYRAZOL-5-YLAMINO)ACETYL]PENTYLCARBAMATE'>FSP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1tu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tu6 OCA], [https://pdbe.org/1tu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tu6 RCSB], [https://www.ebi.ac.uk/pdbsum/1tu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tu6 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == 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 == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tu/1tu6_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tu/1tu6_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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==See Also== | ==See Also== | ||
*[[Cathepsin|Cathepsin]] | *[[Cathepsin 3D structures|Cathepsin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Barrett | [[Category: Barrett DG]] | ||
[[Category: Catalano | [[Category: Catalano JG]] | ||
[[Category: Deaton | [[Category: Deaton DN]] | ||
[[Category: Hassell | [[Category: Hassell AM]] | ||
[[Category: Long | [[Category: Long ST]] | ||
[[Category: Miller | [[Category: Miller AB]] | ||
[[Category: Miller | [[Category: Miller LR]] | ||
[[Category: Shewchuk | [[Category: Shewchuk LM]] | ||
[[Category: Wells-Knecht | [[Category: Wells-Knecht KJ]] | ||
[[Category: Wright | [[Category: Wright LL]] | ||
Latest revision as of 03:32, 21 November 2024
Cathepsin K complexed with a ketoamide inhibitorCathepsin K complexed with a ketoamide inhibitor
Structural highlights
DiseaseCATK_HUMAN Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.[1] [2] [3] [4] FunctionCATK_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P(2) substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P(3), P(1), and P(1') moieties afforded orally bioavailable inhibitors. Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions.,Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL Bioorg Med Chem Lett. 2004 Oct 4;14(19):4897-902. PMID:15341947[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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