Sandbox 34: Difference between revisions
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=== Catalytic Mechanism === | === Catalytic Mechanism === | ||
The mechanism of cysteine proteases is very similar to that of serine proteases. The sulfhydryl group on cysteine executes a nucleophilic attack on the peptide bond of the protein it wishes to cleave. Opening up the carbonyl, the sulfhydryl group of CYS-25 is stabilized by HIS-159. As the carbonyl reforms, the peptide bond is broken, leaving the amide group to fend for itself.<ref>[http://chemistry.umeche.maine.edu/CHY431/Peptidase10.html] University of Maine</ref> [[Image:Papainmech6.jpg|200px|left|thumb| General mechanism of papain catalysis<ref>[http://chemistry.umeche.maine.edu/CHY431/Peptidase10.html] University of Maine</ref>.]] | The mechanism of cysteine proteases is very similar to that of serine proteases. The sulfhydryl group on cysteine executes a nucleophilic attack on the peptide bond of the protein it wishes to cleave. Asparagine-175 keeps histidine-159 in its stabilized imidazole form, while both histidine-159 and cysteine-25 take part in the actual mechanism. Opening up the carbonyl, the sulfhydryl group of CYS-25 is stabilized by HIS-159. As the carbonyl reforms, the peptide bond is broken, leaving the amide group to fend for itself.<ref>[http://chemistry.umeche.maine.edu/CHY431/Peptidase10.html] University of Maine</ref> [[Image:Papainmech6.jpg|200px|left|thumb| General mechanism of papain catalysis<ref>[http://chemistry.umeche.maine.edu/CHY431/Peptidase10.html] University of Maine</ref>.]] | ||
=== Inhibitors === | === Inhibitors === | ||
There are many inhibitors for papain because of its broad specificity. The inhibition of papain is usually due to active site restriction. An interesting inhibitor is that of <scene name='Sandbox_34/Clik148_inhibitor/1'>Clik148</scene>. This inhibitor uses both prime and non-prime sites to inhibit papain.<ref> PMID:10600517 </ref> | There are many inhibitors for papain because of its broad specificity. It is often used as a model enzyme for those in the papain superfamily, such as cathepsin L and cathepsin K. The inhibition of papain is usually due to active site restriction of cysteine-25 and histidine-159. An interesting inhibitor for cathepsin L developed using papain as the model protease is that of <scene name='Sandbox_34/Clik148_inhibitor/1'>Clik148</scene>. This inhibitor uses both prime and non-prime sites to inhibit papain.<ref> PMID:10600517 </ref> | ||
