1ayv: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1ayv.jpg|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1ayv", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_1ayv|  PDB=1ayv  |  SCENE=  }}
-'''CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT THIAZOLHYDRAZIDE INHIBITOR'''
+==CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT THIAZOLHYDRAZIDE INHIBITOR==
+<StructureSection load='1ayv' size='340' side='right'caption='[[1ayv]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1ayv]] 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=1AYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AYV 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IN6:N-[2-[1-(N-BENZYLOXYCARBONYLAMINO)-3-METHYLBUTYL]THIAZOL-4-YLCARBONYL]-N-(BENZYLOXYCARBONYL-L-LEUCINYL)HYDRAZIDE'>IN6</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=1ayv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ayv OCA], [https://pdbe.org/1ayv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ayv RCSB], [https://www.ebi.ac.uk/pdbsum/1ayv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ayv 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/ay/1ayv_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=1ayv ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Potent and selective active-site-spanning inhibitors have been designed for cathepsin K, a cysteine protease unique to osteoclasts. They act by mechanisms that involve tight binding intermediates, potentially on a hydrolytic pathway. X-ray crystallographic, MS, NMR spectroscopic, and kinetic studies of the mechanisms of inhibition indicate that different intermediates or transition states are being represented that are dependent on the conditions of measurement and the specific groups flanking the carbonyl in the inhibitor. The species observed crystallographically are most consistent with tetrahedral intermediates that may be close approximations of those that occur during substrate hydrolysis. Initial kinetic studies suggest the possibility of irreversible and reversible active-site modification. Representative inhibitors have demonstrated antiresorptive activity both in vitro and in vivo and therefore are promising leads for therapeutic agents for the treatment of osteoporosis. Expansion of these inhibitor concepts can be envisioned for the many other cysteine proteases implicated for therapeutic intervention.
-==Overview==
+Design of potent and selective human cathepsin K inhibitors that span the active site.,Thompson SK, Halbert SM, Bossard MJ, Tomaszek TA, Levy MA, Zhao B, Smith WW, Abdel-Meguid SS, Janson CA, D'Alessio KJ, McQueney MS, Amegadzie BY, Hanning CR, DesJarlais RL, Briand J, Sarkar SK, Huddleston MJ, Ijames CF, Carr SA, Garnes KT, Shu A, Heys JR, Bradbeer J, Zembryki D, Lee-Rykaczewski L, James IE, Lark MW, Drake FH, Gowen M, Gleason JG, Veber DF Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14249-54. PMID:9405598<ref>PMID:9405598</ref>
-Potent and selective active-site-spanning inhibitors have been designed for cathepsin K, a cysteine protease unique to osteoclasts. They act by mechanisms that involve tight binding intermediates, potentially on a hydrolytic pathway. X-ray crystallographic, MS, NMR spectroscopic, and kinetic studies of the mechanisms of inhibition indicate that different intermediates or transition states are being represented that are dependent on the conditions of measurement and the specific groups flanking the carbonyl in the inhibitor. The species observed crystallographically are most consistent with tetrahedral intermediates that may be close approximations of those that occur during substrate hydrolysis. Initial kinetic studies suggest the possibility of irreversible and reversible active-site modification. Representative inhibitors have demonstrated antiresorptive activity both in vitro and in vivo and therefore are promising leads for therapeutic agents for the treatment of osteoporosis. Expansion of these inhibitor concepts can be envisioned for the many other cysteine proteases implicated for therapeutic intervention.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-AYV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AYV OCA].
+</div>
+<div class="pdbe-citations 1ayv" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Design of potent and selective human cathepsin K inhibitors that span the active site., Thompson SK, Halbert SM, Bossard MJ, Tomaszek TA, Levy MA, Zhao B, Smith WW, Abdel-Meguid SS, Janson CA, D'Alessio KJ, McQueney MS, Amegadzie BY, Hanning CR, DesJarlais RL, Briand J, Sarkar SK, Huddleston MJ, Ijames CF, Carr SA, Garnes KT, Shu A, Heys JR, Bradbeer J, Zembryki D, Lee-Rykaczewski L, James IE, Lark MW, Drake FH, Gowen M, Gleason JG, Veber DF, Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14249-54. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9405598 9405598]
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
-[[Category: Cathepsin K]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Abdel-Meguid, S S.]]
+[[Category: Abdel-Meguid SS]]
-[[Category: Janson, C A.]]
+[[Category: Janson CA]]
-[[Category: Smith, W W.]]
+[[Category: Smith WW]]
-[[Category: Zhao, B.]]
+[[Category: Zhao B]]
-[[Category: Hydrolase]]
-[[Category: Sulfhydryl proteinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 10:51:34 2008''