1kxr
From Proteopedia
(New page: 200px<br /><applet load="1kxr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kxr, resolution 2.07Å" /> '''Crystal Structure of...) |
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| - | [[Image:1kxr.gif|left|200px]]<br /><applet load="1kxr" size=" | + | [[Image:1kxr.gif|left|200px]]<br /><applet load="1kxr" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kxr, resolution 2.07Å" /> | caption="1kxr, resolution 2.07Å" /> | ||
'''Crystal Structure of Calcium-Bound Protease Core of Calpain I'''<br /> | '''Crystal Structure of Calcium-Bound Protease Core of Calpain I'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ca(2+) signaling by calpains leads to controlled proteolysis during | + | Ca(2+) signaling by calpains leads to controlled proteolysis during processes ranging from cytoskeleton remodeling in mammals to sex determination in nematodes. Deregulated Ca(2+) levels result in aberrant proteolysis by calpains, which contributes to tissue damage in heart and brain ischemias as well as neurodegeneration in Alzheimer's disease. Here we show that activation of the protease core of mu calpain requires cooperative binding of two Ca(2+) atoms at two non-EF-hand sites revealed in the 2.1 A crystal structure. Conservation of the Ca(2+) binding residues defines an ancestral general mechanism of activation for most calpain isoforms, including some that lack EF-hand domains. The protease region is not affected by the endogenous inhibitor, calpastatin, and may contribute to calpain-mediated pathologies when the core is released by autoproteolysis. |
==About this Structure== | ==About this Structure== | ||
| - | 1KXR 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:// | + | 1KXR 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=1KXR 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: Elce, J | + | [[Category: Elce, J S.]] |
| - | [[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 novel cooperative calcium sites]] | [[Category: two novel cooperative calcium sites]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:39:08 2008'' |
Revision as of 11:39, 21 February 2008
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Crystal Structure of Calcium-Bound Protease Core of Calpain I
Overview
Ca(2+) signaling by calpains leads to controlled proteolysis during processes ranging from cytoskeleton remodeling in mammals to sex determination in nematodes. Deregulated Ca(2+) levels result in aberrant proteolysis by calpains, which contributes to tissue damage in heart and brain ischemias as well as neurodegeneration in Alzheimer's disease. Here we show that activation of the protease core of mu calpain requires cooperative binding of two Ca(2+) atoms at two non-EF-hand sites revealed in the 2.1 A crystal structure. Conservation of the Ca(2+) binding residues defines an ancestral general mechanism of activation for most calpain isoforms, including some that lack EF-hand domains. The protease region is not affected by the endogenous inhibitor, calpastatin, and may contribute to calpain-mediated pathologies when the core is released by autoproteolysis.
About this Structure
1KXR 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
A Ca(2+) switch aligns the active site of calpain., Moldoveanu T, Hosfield CM, Lim D, Elce JS, Jia Z, Davies PL, Cell. 2002 Mar 8;108(5):649-60. PMID:11893336
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