Sandbox 34: Difference between revisions
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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> In two different cathepsin K inhibitors, referenced PDB codes <scene name='Sandbox_34/Cathepsin_k_1bp4/1'>1BP4</scene> and <scene name='Sandbox_34/Cathepsin_k_1bqi/1'>1BQI</scene>, it is evident that the inhibitor binds with much closer proximity than that of Clik148.<ref> PMID:9804696 </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> In two different cathepsin K inhibitors, referenced PDB codes <scene name='Sandbox_34/Cathepsin_k_1bp4/1'>1BP4</scene> and <scene name='Sandbox_34/Cathepsin_k_1bqi/1'>1BQI</scene>, it is evident that the inhibitor binds with much closer proximity than that of Clik148.<ref> PMID:9804696 </ref> | ||
Other inhibitors, such as <scene name='Sandbox_34/Pap_1stf/1'>human stefin B</scene>, illustrated in magenta, are much more complex in their <scene name='Sandbox_34/Pap_1stf/2'>inhibition</scene>. The human stefin B molecule has a five stranded beta-sheet that wraps around a five turn alpha-helix. The interface between human stefin B and papain is very tightly packed with 16% of stefin B becoming embedded within papain. A total of 128 <scene name='Sandbox_34/Pap_1stf/4'>intermolecular atom-atom interactions</scene> <4 A occur within the cleft in papain, although only CYS25 interacts with the inhibitor. In this figure, the residues of interaction for stefin B are shown in blue, the residues of interaction for papain are shown in red, and the residues of papain's active site are shown in green. Through this study, Stubbs et al. were able to conclude that cysteine proteinase inhibitors are "fundamentally different to [those] observed for serine proteinase inhibitors."<ref>PMID:2347312</ref> | |||
<scene name='Sandbox_34/Pap_1stf/ | |||
