1df0: Difference between revisions
New page: left|200px<br /><applet load="1df0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1df0, resolution 2.6Å" /> '''CRYSTAL STRUCTURE OF ... |
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[[Image:1df0.gif|left|200px]]<br /><applet load="1df0" size=" | [[Image:1df0.gif|left|200px]]<br /><applet load="1df0" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1df0, resolution 2.6Å" /> | caption="1df0, resolution 2.6Å" /> | ||
'''CRYSTAL STRUCTURE OF M-CALPAIN'''<br /> | '''CRYSTAL STRUCTURE OF M-CALPAIN'''<br /> | ||
==Overview== | ==Overview== | ||
The combination of thiol protease activity and calmodulin-like EF-hands is | The combination of thiol protease activity and calmodulin-like EF-hands is a feature unique to the calpains. The regulatory mechanisms governing calpain activity are complex, and the nature of the Ca(2+)-induced switch between inactive and active forms has remained elusive in the absence of structural information. We describe here the 2.6 A crystal structure of m-calpain in the Ca(2+)-free form, which illustrates the structural basis for the inactivity of calpain in the absence of Ca(2+). It also reveals an unusual thiol protease fold, which is associated with Ca(2+)-binding domains through heterodimerization and a C(2)-like beta-sandwich domain. Strikingly, the structure shows that the catalytic triad is not assembled, indicating that Ca(2+)-binding must induce conformational changes that re-orient the protease domains to form a functional active site. The alpha-helical N-terminal anchor of the catalytic subunit does not occupy the active site but inhibits its assembly and regulates Ca(2+)-sensitivity through association with the regulatory subunit. This Ca(2+)-dependent activation mechanism is clearly distinct from those of classical proteases. | ||
==About this Structure== | ==About this Structure== | ||
1DF0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 and 3.4.22.53 3.4.22.52 and 3.4.22.53] Full crystallographic information is available from [http:// | 1DF0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 and 3.4.22.53 3.4.22.52 and 3.4.22.53] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DF0 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Davies, P | [[Category: Davies, P L.]] | ||
[[Category: Elce, J | [[Category: Elce, J S.]] | ||
[[Category: Hosfield, C | [[Category: Hosfield, C M.]] | ||
[[Category: Jia, Z.]] | [[Category: Jia, Z.]] | ||
[[Category: c2 domain]] | [[Category: c2 domain]] | ||
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[[Category: zymogen activation]] | [[Category: zymogen activation]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:15:57 2008'' | ||
Revision as of 13:15, 21 February 2008
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CRYSTAL STRUCTURE OF M-CALPAIN
OverviewOverview
The combination of thiol protease activity and calmodulin-like EF-hands is a feature unique to the calpains. The regulatory mechanisms governing calpain activity are complex, and the nature of the Ca(2+)-induced switch between inactive and active forms has remained elusive in the absence of structural information. We describe here the 2.6 A crystal structure of m-calpain in the Ca(2+)-free form, which illustrates the structural basis for the inactivity of calpain in the absence of Ca(2+). It also reveals an unusual thiol protease fold, which is associated with Ca(2+)-binding domains through heterodimerization and a C(2)-like beta-sandwich domain. Strikingly, the structure shows that the catalytic triad is not assembled, indicating that Ca(2+)-binding must induce conformational changes that re-orient the protease domains to form a functional active site. The alpha-helical N-terminal anchor of the catalytic subunit does not occupy the active site but inhibits its assembly and regulates Ca(2+)-sensitivity through association with the regulatory subunit. This Ca(2+)-dependent activation mechanism is clearly distinct from those of classical proteases.
About this StructureAbout this Structure
1DF0 is a Protein complex structure of sequences from Rattus norvegicus. Active as Hydrolase, with EC number and 3.4.22.53 3.4.22.52 and 3.4.22.53 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation., Hosfield CM, Elce JS, Davies PL, Jia Z, EMBO J. 1999 Dec 15;18(24):6880-9. PMID:10601010
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