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Delineation of chicken cathepsin L secondary structure; relationship between pH dependence activity and helix content

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Abstract

The secondary structure of the recently sequenced chicken liver cathepsin L (EC 3.4.22.15) has been studied both by circular dichroism and a predictive method. The structural data provided by these approaches allow us to underline the extent of the structural similarities between cathepsin L and papain, one of the best known proteins in the cysteine proteinase family. The predictive method of Garnier et al. (J. Mol. Biol. 120 (1978) 97–120) is used to locate α-helix and β-sheet segments in the cathepsin L sequence. An optimization of decision constants has been performed, using circular dichroism data, to improve good predictions. The combination of these approaches lead us to suggest that the location of ordered structures observed in papain is maintained in cathepsin L, but with an additional α-helix in the middle region (residues 85–108) of cathepsin L. Furthermore, we show that cathepsin L inactivation at neutral pH is correlated to the lost of α-helix content (40% at pH 5.8 and 17% at pH 7.0) in this protein. It appears that such an effect can be related to the change in the ionization state of histidine side-chains which are shown to be mainly located in the predicted α-helix regions.

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    Although the binding site of GAGs and the prosegment on the TPP I molecule appear to partially overlap, the binding of GAGs was not saturable, and the interaction of the prosegment with its cognate enzyme was tight and saturable. It was documented that alkaline pH-induced inactivation of chicken cathepsin L was accompanied by the loss of α-helical content (35). Thus, it is reasonable to propose that the TPP I prosegment, by tightly binding its parent protease, might stabilize the activity of TPP I at alkaline pH by preventing pH-induced unfolding of the protein.

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