1mdw
From Proteopedia
(New page: 200px<br /><applet load="1mdw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mdw, resolution 1.95Å" /> '''Crystal Structure of...) |
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| - | [[Image:1mdw.gif|left|200px]]<br /><applet load="1mdw" size=" | + | [[Image:1mdw.gif|left|200px]]<br /><applet load="1mdw" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1mdw, resolution 1.95Å" /> | caption="1mdw, resolution 1.95Å" /> | ||
'''Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation'''<br /> | '''Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Uncontrolled activation of calpain can lead to necrotic cell death and | + | Uncontrolled activation of calpain can lead to necrotic cell death and irreversible tissue damage. We have discovered an intrinsic mechanism whereby the autolysis-generated protease core fragment of calpain is inactivated through the inherent instability of a key alpha-helix. This auto-inactivation state was captured by the 1.9 A Ca(2+)-bound structure of the protease core from m-calpain, and sequence alignments suggest that it applies to about half of the calpain isoforms. Intact calpain large subunits are also subject to this inhibition, which can be prevented through assembly of the heterodimers. Other isoforms or their released cores are not silenced by this mechanism and might contribute to calpain patho-physiologies. |
==About this Structure== | ==About this Structure== | ||
| - | 1MDW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1MDW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1MDW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Davies, P | + | [[Category: Davies, P L.]] |
| - | [[Category: Hosfield, C | + | [[Category: Hosfield, C M.]] |
[[Category: Jia, Z.]] | [[Category: Jia, Z.]] | ||
[[Category: Lim, D.]] | [[Category: Lim, D.]] | ||
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[[Category: two cooperative calcium sites]] | [[Category: two cooperative calcium sites]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:14 2008'' |
Revision as of 11:54, 21 February 2008
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Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation
Overview
Uncontrolled activation of calpain can lead to necrotic cell death and irreversible tissue damage. We have discovered an intrinsic mechanism whereby the autolysis-generated protease core fragment of calpain is inactivated through the inherent instability of a key alpha-helix. This auto-inactivation state was captured by the 1.9 A Ca(2+)-bound structure of the protease core from m-calpain, and sequence alignments suggest that it applies to about half of the calpain isoforms. Intact calpain large subunits are also subject to this inhibition, which can be prevented through assembly of the heterodimers. Other isoforms or their released cores are not silenced by this mechanism and might contribute to calpain patho-physiologies.
About this Structure
1MDW is a Single protein structure of sequence from Rattus norvegicus with as ligand. 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.
Reference
Calpain silencing by a reversible intrinsic mechanism., Moldoveanu T, Hosfield CM, Lim D, Jia Z, Davies PL, Nat Struct Biol. 2003 May;10(5):371-8. PMID:12665854
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