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1zcm

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[[Image:1zcm.gif|left|200px]]<br /><applet load="1zcm" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1zcm.gif|left|200px]]
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caption="1zcm, resolution 2.0&Aring;" />
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'''Human calpain protease core inhibited by ZLLYCH2F'''<br />
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{{Structure
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|PDB= 1zcm |SIZE=350|CAPTION= <scene name='initialview01'>1zcm</scene>, resolution 2.0&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=C1N:N-[(BENZYLOXY)CARBONYL]LEUCYL-N~1~-[3-FLUORO-1-(4-HYDROXYBENZYL)-2-OXOPROPYL]LEUCINAMIDE'>C1N</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Calpain-1 Calpain-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 3.4.22.52]
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|GENE= CAPN1, CANPL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Human calpain protease core inhibited by ZLLYCH2F'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1ZCM 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 <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=C1N:'>C1N</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Calpain-1 Calpain-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 3.4.22.52] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZCM OCA].
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1ZCM 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=1ZCM OCA].
==Reference==
==Reference==
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Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core., Li Q, Hanzlik RP, Weaver RF, Schonbrunn E, Biochemistry. 2006 Jan 24;45(3):701-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16411745 16411745]
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Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core., Li Q, Hanzlik RP, Weaver RF, Schonbrunn E, Biochemistry. 2006 Jan 24;45(3):701-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16411745 16411745]
[[Category: Calpain-1]]
[[Category: Calpain-1]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: thiol protease]]
[[Category: thiol protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:20 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:33:51 2008''

Revision as of 13:33, 20 March 2008

Image:1zcm.gif


PDB ID 1zcm

Drag the structure with the mouse to rotate
, resolution 2.0Å
Ligands: and
Gene: CAPN1, CANPL1 (Homo sapiens)
Activity: Calpain-1, with EC number 3.4.22.52
Coordinates: save as pdb, mmCIF, xml



Human calpain protease core inhibited by ZLLYCH2F


Contents

Overview

Calpain is a nearly ubiquitous Ca2+-activated proteolytic enzyme whose precise physiological function is unknown. However, aberrant Ca2+ homeostasis in the course of cellular injuries and certain diseases of the CNS appears to activate calpain, in turn promoting the degradation of key cytoskeletal and membrane proteins. Hyperactive calpain has also been implicated in various aging phenomena and diseases of late life. Therefore, calpain is considered a potential therapeutic target in preventing degenerations of many kinds. Despite its potential medicinal importance, known structural information about mu-calpain is limited to that from the rat enzyme. We have determined the crystal structure of the human mu-calpain protease core (hmuI-II) containing a Gly213Ala mutation and covalently inactivated by a peptidomimetic (ZLLYCH2F) at 2.0 A resolution. The methylene carbon of the inhibitor is bound to Cys115. Additional hydrogen bonding and hydrophobic interactions between active site residues and the inhibitor, including an intermolecular antiparallel beta-sheet arrangement characteristically observed with members of the papain family of cysteine proteinases, help to stabilize the complex and orient the inhibitor. The terminal ZL portion of the inhibitor is solvent-exposed and highly flexible, and is thus not involved in specific binding interactions with the enzyme. Two large enzyme regions flanking the active site are highly flexible; they may be important in recognition of calpain's natural protein substrates and in positioning them for catalysis. The implications for drug design are discussed.

Disease

Known disease associated with this structure: Diabetes mellitus, noninsulin-dependent OMIM:[605286]

About this Structure

1ZCM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core., Li Q, Hanzlik RP, Weaver RF, Schonbrunn E, Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745

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