The Heavy-Light Chain Loop of Human Cathepsin-L Modulates Its Activity and Stability

Title: The Heavy-Light Chain Loop of Human Cathepsin-L Modulates Its Activity and Stability

Volume: 15 Issue: 1

Author(s): Christopher F. van der Walle and Michael Fairhead

Affiliation:

Keywords: Cathepsin-L, Silicatein-α, cysteine protease, protein engineering

Abstract: Differences evident in the sequence alignment of human cathepsin-L with shrimp cathepsin-L and silicatein-α suggest the indirect involvement of the heavy to light chain loop (E286 to E289) in the function of these enzymes. Deletion of the loop and adjacent residues S290 to N293, decreased specific protease activity by 81% and 63%, respectively; complete substitution for the corresponding silicatein-α loop decreased activity by 35%. In all cases the Km was largely unchanged. The conformational stability of human procathepsin-L was not altered by deletion of E286 to E289 but increased on deletion of S290 to N293. Therefore, shortening the loop does not change substrate affinity but does influence activity, in part via conformational change.

Cite this article as:

van der Walle F. Christopher and Fairhead Michael, The Heavy-Light Chain Loop of Human Cathepsin-L Modulates Its Activity and Stability, Protein & Peptide Letters 2008; 15 (1) . https://dx.doi.org/10.2174/092986608783330468