1tl9: Difference between revisions
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New page: left|200px<br /><applet load="1tl9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tl9, resolution 1.80Å" /> '''High resolution crys... |
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== | ==High resolution crystal structure of calpain I protease core in complex with leupeptin== | ||
The endogenous calpain inhibitor, calpastatin, modulates some | <StructureSection load='1tl9' size='340' side='right'caption='[[1tl9]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1tl9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Streptomyces_roseus Streptomyces roseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TL9 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AR7:AMINO{[(4S)-4-AMINO-5,5-DIHYDROXYPENTYL]AMINO}METHANIMINIUM'>AR7</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1tl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tl9 OCA], [https://pdbe.org/1tl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tl9 RCSB], [https://www.ebi.ac.uk/pdbsum/1tl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tl9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAN1_RAT CAN1_RAT] Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. | |||
== 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/tl/1tl9_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=1tl9 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The endogenous calpain inhibitor, calpastatin, modulates some patho-physiological aspects of calpain signaling. Excess calpain can escape this inhibition and as well, many calpain isoforms and autolytically generated protease core fragments are not inhibited by calpastatin. There is a need, therefore, to develop specific, cell-permeable calpain inhibitors to block uncontrolled proteolysis and prevent tissue damage during brain and heart ischemia, spinal-cord injury and Alzheimer's diseases. Here, we report the first high-resolution crystal structures of rat mu-calpain protease core complexed with two traditional, low molecular mass inhibitors, leupeptin and E64. These structures show that access to a slightly deeper, but otherwise papain-like active site is gated by two flexible loops. These loops are divergent among the calpain isoforms giving a potential structural basis for substrate/inhibitor selectivity over other papain-like cysteine proteases and between members of the calpain family. | |||
Crystal structures of calpain-E64 and -leupeptin inhibitor complexes reveal mobile loops gating the active site.,Moldoveanu T, Campbell RL, Cuerrier D, Davies PL J Mol Biol. 2004 Nov 5;343(5):1313-26. PMID:15491615<ref>PMID:15491615</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1tl9" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Calpain 3D structures|Calpain 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: | [[Category: Streptomyces roseus]] | ||
[[Category: Campbell | [[Category: Campbell RL]] | ||
[[Category: Cuerrier | [[Category: Cuerrier D]] | ||
[[Category: Davies | [[Category: Davies PL]] | ||
[[Category: Moldoveanu | [[Category: Moldoveanu T]] | ||
Latest revision as of 00:31, 21 November 2024
High resolution crystal structure of calpain I protease core in complex with leupeptin
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