1tu6: Difference between revisions

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OCA

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-[[Image:1tu6.gif|left|200px]]<br />
-<applet load="1tu6" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1tu6, resolution 1.75&Aring;" />
-'''Cathepsin K complexed with a ketoamide inhibitor'''<br />
-==Overview==
+==Cathepsin K complexed with a ketoamide inhibitor==
-A 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.
+<StructureSection load='1tu6' size='340' side='right'caption='[[1tu6]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</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>
+</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/tu/1tu6_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=1tu6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A 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.
-==Disease==
+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<ref>PMID:15341947</ref>
-Known disease associated with this structure: Pycnodysostosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601105 601105]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-TU6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and FSP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TU6 OCA].
+</div>
+<div class="pdbe-citations 1tu6" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15341947 15341947]
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-[[Category: Cathepsin K]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Barrett, D.G.]]
+[[Category: Barrett DG]]
-[[Category: Catalano, J.G.]]
+[[Category: Catalano JG]]
-[[Category: Deaton, D.N.]]
+[[Category: Deaton DN]]
-[[Category: Hassell, A.M.]]
+[[Category: Hassell AM]]
-[[Category: Long, S.T.]]
+[[Category: Long ST]]
-[[Category: Miller, A.B.]]
+[[Category: Miller AB]]
-[[Category: Miller, L.R.]]
+[[Category: Miller LR]]
-[[Category: Shewchuk, L.M.]]
+[[Category: Shewchuk LM]]
-[[Category: Wells-Knecht, K.J.]]
+[[Category: Wells-Knecht KJ]]
-[[Category: Wright, L.L.]]
+[[Category: Wright LL]]
-[[Category: FSP]]
-[[Category: SO4]]
-[[Category: catk]]
-[[Category: cysteine protease]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:28:13 2007''