1u5i
From Proteopedia
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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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