1u5i
From Proteopedia
(New page: 200px<br /><applet load="1u5i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u5i, resolution 2.86Å" /> '''Crystal Structure an...) |
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| - | [[Image:1u5i.gif|left|200px]]<br /><applet load="1u5i" size=" | + | [[Image:1u5i.gif|left|200px]]<br /><applet load="1u5i" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1u5i, resolution 2.86Å" /> | caption="1u5i, resolution 2.86Å" /> | ||
'''Crystal Structure analysis of rat m-calpain mutant Lys10 Thr'''<br /> | '''Crystal Structure analysis of rat m-calpain mutant Lys10 Thr'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The calpains are a family of cysteine proteases with closely related amino | + | The calpains are a family of cysteine proteases with closely related amino acid sequences, but a wide range of Ca(2+) requirements (K(d)). For m-calpain, K(d) is approximately 325microM, for mu-calpain it is approximately 50microM, and for calpain 3 it is not strictly known but may be approximately 0.1microM. On the basis of previous structure determination of m-calpain we postulated that two regions of the calpain large subunits, the N-terminal peptide (residues 1-20) and a domain III-IV linker peptide (residues 514-530 in m-calpain) were important in defining K(d). The mutations Lys10Thr in the N-terminal peptide, and Glu517Pro in the domain linker peptide, reduced K(d) of m-calpain by 30% and 42%, respectively, revealing that these two regions are functionally important. The increased Ca(2+)-sensitivity of these mutants demonstrate that the Lys10-Asp148 salt link and the short beta-sheet interaction involving Glu517 are factors contributing to the high K(d) of m-calpain. Though these two regions are physically remote from the active site and Ca(2+)-binding site, they play significant roles in regulating the response of calpain to Ca(2+). Differences in these interactions in mu-calpain and in calpain 3 are also consistent with their progressively lower K(d) values. |
==About this Structure== | ==About this Structure== | ||
| - | 1U5I 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/Calpain-2 Calpain-2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.53 3.4.22.53] Full crystallographic information is available from [http:// | + | 1U5I 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/Calpain-2 Calpain-2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.53 3.4.22.53] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U5I OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Elce, J | + | [[Category: Elce, J S.]] |
| - | [[Category: Hosfield, C | + | [[Category: Hosfield, C M.]] |
[[Category: Jia, Z.]] | [[Category: Jia, Z.]] | ||
| - | [[Category: Pal, G | + | [[Category: Pal, G P.]] |
[[Category: calpain]] | [[Category: calpain]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
[[Category: sulfhydryl protease]] | [[Category: sulfhydryl protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:20:46 2008'' |
Revision as of 13:20, 21 February 2008
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Crystal Structure analysis of rat m-calpain mutant Lys10 Thr
Overview
The calpains are a family of cysteine proteases with closely related amino acid sequences, but a wide range of Ca(2+) requirements (K(d)). For m-calpain, K(d) is approximately 325microM, for mu-calpain it is approximately 50microM, and for calpain 3 it is not strictly known but may be approximately 0.1microM. On the basis of previous structure determination of m-calpain we postulated that two regions of the calpain large subunits, the N-terminal peptide (residues 1-20) and a domain III-IV linker peptide (residues 514-530 in m-calpain) were important in defining K(d). The mutations Lys10Thr in the N-terminal peptide, and Glu517Pro in the domain linker peptide, reduced K(d) of m-calpain by 30% and 42%, respectively, revealing that these two regions are functionally important. The increased Ca(2+)-sensitivity of these mutants demonstrate that the Lys10-Asp148 salt link and the short beta-sheet interaction involving Glu517 are factors contributing to the high K(d) of m-calpain. Though these two regions are physically remote from the active site and Ca(2+)-binding site, they play significant roles in regulating the response of calpain to Ca(2+). Differences in these interactions in mu-calpain and in calpain 3 are also consistent with their progressively lower K(d) values.
About this Structure
1U5I is a Protein complex structure of sequences from Rattus norvegicus. Active as Calpain-2, with EC number 3.4.22.53 Full crystallographic information is available from OCA.
Reference
Activation of calpain by Ca2+: roles of the large subunit N-terminal and domain III-IV linker peptides., Hosfield CM, Elce JS, Jia Z, J Mol Biol. 2004 Oct 29;343(4):1049-53. PMID:15476820
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