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| - | [[Image:1zcm.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1zcm| PDB=1zcm | SCENE= }} | | {{STRUCTURE_1zcm| PDB=1zcm | SCENE= }} |
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| - | '''Human calpain protease core inhibited by ZLLYCH2F'''
| + | ===Human calpain protease core inhibited by ZLLYCH2F=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16411745}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16411745 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16411745}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Protease]] | | [[Category: Protease]] |
| | [[Category: Thiol protease]] | | [[Category: Thiol protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:27:59 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:00:12 2008'' |
Revision as of 04:00, 29 July 2008
Template:STRUCTURE 1zcm
Human calpain protease core inhibited by ZLLYCH2F
Template:ABSTRACT PUBMED 16411745
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
Page seeded by OCA on Tue Jul 29 07:00:12 2008
