Sandbox 39: Difference between revisions
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== Papain Inhibition == | == Papain Inhibition == | ||
<Structure load='9pap' size='300' frame='true' align='right' caption='Papain/ZLFG-DAM covalent complex' scene=''/> | |||
Substances that inhibit enzymes have sequences that resemble the normal substrate of that enzyme. Some substances that act to inhibit the enzymatic activity of papain are able to do so because of their structural and chemical similarity to polypeptides normally degraded by papain. | Substances that inhibit enzymes have sequences that resemble the normal substrate of that enzyme. Some substances that act to inhibit the enzymatic activity of papain are able to do so because of their structural and chemical similarity to polypeptides normally degraded by papain. | ||
One example of a papain inhibitor is cystatin. According to this model, the N terminal of the cystatin interacts with the active site and the S1-S3 sites of papain. At the same time, two hairpin loops bind to the S1’-S2’ sites. The interaction between systatin and papain can be seen below. The inactivation of the cysteine proteases, including papain, occurs by competitive, noncovalent, reversible inhibition. | One example of a papain inhibitor is cystatin. According to this model, the N terminal of the cystatin interacts with the active site and the S1-S3 sites of papain. At the same time, two hairpin loops bind to the S1’-S2’ sites. The interaction between systatin and papain can be seen below. The inactivation of the cysteine proteases, including papain, occurs by competitive, noncovalent, reversible inhibition. | ||
Another example of a papain inhibitor is <scene name='Sandbox_39/Inhibitor_revised/1'>ZLFG-DAM</scene>, a diazomethylketone inhibitor. As shown in the Jmol to the right, the methylene carbon atom of the inhibitor (shown as a grey sphere), is covalently bound to the Cys-25 of papain. The hydrophobic S2 pocket is occupied by the inhibitor's P2 side chain, shown as a pink chain. Extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. | Another example of a papain inhibitor is <scene name='Sandbox_39/Inhibitor_revised/1'>ZLFG-DAM</scene>, a diazomethylketone inhibitor. As shown in the Jmol to the right, the methylene carbon atom of the inhibitor (shown as a grey sphere), is covalently bound to the Cys-25 of papain. The hydrophobic S2 pocket is occupied by the inhibitor's P2 side chain, shown as a pink chain. Extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. | ||
Several other molecules have been shown to have protease inhibitory actions. Leupeptin is a naturally-occuring, microbial protease inhibitor. Shown | Several other molecules have been shown to have protease inhibitory actions. Leupeptin is a naturally-occuring, microbial protease inhibitor. Shown below, sitting in the active site of papain, this molecule contains an arginine residue at its C-terminus that is essential for its inhibitory action. | ||
[[Image:Leupeptin.jpg | Antipain, a protease specific to papain and trypsin, is a microbial product isolated from actinomycetes. This inhibitor contains a catalytic aldehyde and acts like leupeptin. Antipain is often used in typical protease inhibitor cocktails. | ||
[[Image:Leupeptin.jpg]] | |||
<ref>Image from: | <ref>Image from: | ||
http://www.rcsb.org/pdb/explore/explore.do?structureId=1POP</ref>]] | http://www.rcsb.org/pdb/explore/explore.do?structureId=1POP</ref>]] | ||
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== References == | == References == | ||
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4. Image from: http://www.rcsb.org/pdb/explore/jmol.do?structureId=9PAP&bionumber=1 | 4. Image from: http://www.rcsb.org/pdb/explore/jmol.do?structureId=9PAP&bionumber=1 | ||
5. Image from: http://www.rcsb.org/pdb/explore/explore.do?structureId=1POP | |||
