Sandbox 34: Difference between revisions
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== Inhibitors == | == Inhibitors == | ||
There are many inhibitors for papain because of its broad specificity. It is often used as a model enzyme for those in the papain | There are many inhibitors for papain because of its broad specificity. It is often used as a model enzyme for those in the papain super-family, such as cathepsin L and cathepsin K. The inhibition of papain is usually due to active site restriction of cysteine-25 and histidine-159. The interest in developing inhibitors for the papain super-family lies with the desire to effectively inhibit other cysteine proteases that incur unfavorable effects within the body. | ||
<Structure load='9pap' size='350' frame='true' align='left' caption='Papain and Inhibition' scene='Sandbox_34/9pap_active_site/1' /> | <Structure load='9pap' size='350' frame='true' align='left' caption='Papain and Inhibition' scene='Sandbox_34/9pap_active_site/1' /> | ||
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===Cathepsin K=== | ===Cathepsin K=== | ||
In two different cathepsin K inhibitors, referenced PDB codes <scene name='Sandbox_34/Cathkaldinhibit/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. 1BP4 is a cathepsin K inhibitor, N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-hydroxy-4-methylpentan-2-yl]-L-leucinamide, that inhibits by interacting with 11 different residues on papain: Gln19, Gly20, Ser21, Gly23, Asn64, Gly65, Gln142, Asp158, His159, Trp177, and Trp181. These interactions range from hydrophobic, electrostatic, and hydrogen bonding, to <scene name='Sandbox_34/Cathkaldinhibitpistacking/1'>ring stacking</scene> between the aromatic ring of the carbobenzyl group on 1BP4, and TRP177 of papain. <ref> PMID:9804696 </ref> | The goal of research for the development of an inhibitor for cathepsin K is the hope to develop a treatment for osteoporosis. In two different cathepsin K inhibitors, referenced PDB codes <scene name='Sandbox_34/Cathkaldinhibit/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. 1BP4 is a cathepsin K inhibitor, N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-hydroxy-4-methylpentan-2-yl]-L-leucinamide, that inhibits by interacting with 11 different residues on papain: Gln19, Gly20, Ser21, Gly23, Asn64, Gly65, Gln142, Asp158, His159, Trp177, and Trp181. These interactions range from hydrophobic, electrostatic, and hydrogen bonding, to <scene name='Sandbox_34/Cathkaldinhibitpistacking/1'>ring stacking</scene> between the aromatic ring of the carbobenzyl group on 1BP4, and TRP177 of papain. The <scene name='Sandbox_34/Cathkketoinhibition/1'>inhibition</scene> of papain by IBQI, carbobenzyloxy-(L)-leucinyl-(L)leucinyl methoxymethylketone, is quite similar to that of IBP4, although it does not bind quite as tightly. It binds to seven residues of papain: Gln19, Gly23, Gly65, Gln142, His159, Trp177, Trp181. Additionally, is has similar | ||
<scene name='Sandbox_34/Cathkketoinhibitionringstackin/1'>ring-stacking</scene> between the Cbz ring on the inhibitor and Trp 177, though it is more difficult to visualize with the given PDB file.<ref> PMID:9804696 </ref> | |||
===Human Stefin B=== | ===Human Stefin B=== | ||
