Papain: Difference between revisions
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==='''Leupeptin'''=== | ==='''Leupeptin'''=== | ||
<scene name='Papain/Leupeptin/4'>Leupeptin</scene> is a commonly studied broad-spectrum competitive protease inhibitor first crystallized by Schröder et. al. It inhibits by binding and interacting with the active site which allows it to block the enzyme's desired protein substrate from binding. There are many <scene name='Papain/Leupeptin_residues/5'>ligand contacts</scene> that interact with Leupeptin, which are predominantly <scene name='Papain/1pop_sam_leupeptin_hydrophobic/ | <scene name='Papain/Leupeptin/4'>Leupeptin</scene> is a commonly studied broad-spectrum competitive protease inhibitor first crystallized by Schröder et. al. It inhibits by binding and interacting with the active site which allows it to block the enzyme's desired protein substrate from binding. There are many <scene name='Papain/Leupeptin_residues/5'>ligand contacts</scene> that interact with Leupeptin, which are predominantly <scene name='Papain/1pop_sam_leupeptin_hydrophobic/5'>hydrophobic</scene> (shown in blue). These residues include tyrosine, tryptophan, and valine, which coordinate the bound Leuptin. Some of the enzyme's residues also make <scene name='Papain/Leupeptin_hbonds/2'>hydrogen bonds</scene>. These hydrogen bonds, shown in white, include interactions between hydrogens on both Gln-19 and the amide nitrogen of the catalytic Cys-25 with the arginal carbanion, forming the catalytically important oxyanion hole. In addition, Gly-66 interacts with the second leucine in Leupeptin while Asp-158 interacts with a hydrogen on the arginal. These interactions further stabilize and orient the substrate in the binding pocket<ref name="Schroder">[http://www.sciencedirect.com/science/article/pii/001457939381128M] Schröder, E., C. Phillips, E. Garman, K. Harlos, C. Crawford. 1997. X-ray crystallographic structure of a papain-leupeptin complex. FEBS Letters 315: 38-42</ref>. | ||
A recent study has shown that Leupeptin forms a covalent bond between its <scene name='Papain/Leupeptin_carbonyl_carbon/1'>carbonyl carbon</scene> and the hydrogen in Cys-25. The inhibitor has the structure Ac-Leu-Leu-Arginal, where Ac is an acetyl group attached to the nitrogen of the first leucine. Cysteine-25, which acts as a catalytic nucleophile, attacks the arginal aldehyde forming a tight-binding transition state from which the normal catalytic mechanism cannot proceed due to this carbonyl having no potential leaving groups bonded to it. | A recent study has shown that Leupeptin forms a covalent bond between its <scene name='Papain/Leupeptin_carbonyl_carbon/1'>carbonyl carbon</scene> and the hydrogen in Cys-25. The inhibitor has the structure Ac-Leu-Leu-Arginal, where Ac is an acetyl group attached to the nitrogen of the first leucine. Cysteine-25, which acts as a catalytic nucleophile, attacks the arginal aldehyde forming a tight-binding transition state from which the normal catalytic mechanism cannot proceed due to this carbonyl having no potential leaving groups bonded to it. | ||