Papain: Difference between revisions

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'''Leupeptin~~'''~~(PDB ID #: 1pop)

'''Leupeptin(PDB ID #: 1pop)'''

<scene name='Sandbox_31/Leupeptin/1'>Leupeptin</scene> is a commonly studied inhibitor of proteases (seen in the Jmol as ball and stick model). It inhibits by binding and interacting with the active site which allows it to block the enzyme's desired protein substrate. There are many <scene name='Sandbox_31/1popligand_contacts/1'>Residues</scene> that interact with Leupeptin in the active site. The predominant interaction is from hydrophobic interactions between Leupeptin and <scene name='Sandbox_31/1pophydrointeract/1'>active site residues</scene>. In addition to hydrophobic interactions, there are also some hydrogen bonding interactions to hold Leupeptin in the active site of papain. Leupeptin works well at blocking papain from its enzymatic duties. A recent study has shown that Leupeptin actually forms a covalent bond between its <scene name='Sandbox_31/Leupeptin_active/1'>Carbonyl Carbon</scene> and CYS 25. In addition, the residues Gln 19 and CYS 25 form <scene name='Sandbox_31/Leupeptin_active/2'>hydrogen bonds</scene> with the Leupeptin molecule

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===Clik-158===

===~~Human Stefin~~ B===

'''Stefin B'''

<scene name='Sandbox_36/Papain_inhibitor_space_fill/1'>Stefin B</scene> acts as a competitive inhibitor to cysteine proteases-- it binds tightly but reversibly to the papain active site. Stefin inhibitors are characterized by M<sub>r</sub> of about 11,000, no disulfide bonds and no associated carbohydrates.

In Stefin B, the Gly9 residue along with two hairpin loops form a "wedge" complementary to the active site groove of papain. This wedge makes extensive and tight interactions with papain and a total of 128 intermolecular atom-atom interactions occur. <scene name='Sandbox_36/Papain_inhibitor_wedge_involve/1'>Residue segments</scene> Met6-Pro11, Gln53-Asn59, Gln101-His104 and Tyr124-Phe125 on the wedge all have some interaction to the enzyme though not always direct. All residues from the base and both sides of the <scene name='Sandbox_36/Papain_inhibitor_activ_involve/1'>active site cleft</scene> are involved in the complex with the inhibtor (Trp177, Ser21, Cys63, Cys25, Asp158 and His159).

There are a small number of <scene name='Sandbox_36/Papain_inhibitor_direct_bond/2'>direct hydrogen bonds</scene> between stefin B and papain, however there are many more polar interactions mediated by <scene name='Sandbox_36/Papain_inhibitor_bridges_inter/1'>solvent bridges</scene>. Thirteen solvent molecules bridge polar residues of the enzyme and inhibitor. Seventeen hydrogen bonds are made with a solvent molecule and stefin. Fourteen of these bridges form a papain contact. The rest of the interactions are largely hydrophobic-- involving apolar <scene name='Sandbox_36/Papain_inhibitor_hydro_inter/2'>Van der Waals interactions</scene>. <ref> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC551902/pdf/emboj00233-0254.pdf </ref>

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@@ Line 35: / Line 35: @@
 <StructureSection load='1pop' size='400' side='left'>
-'''Leupeptin'''(PDB ID #: 1pop)
+'''Leupeptin(PDB ID #: 1pop)'''
 <scene name='Sandbox_31/Leupeptin/1'>Leupeptin</scene> is a commonly studied inhibitor of proteases (seen in the Jmol as ball and stick model).  It inhibits by binding and interacting with the active site which allows it to block the enzyme's desired protein substrate.  There are many <scene name='Sandbox_31/1popligand_contacts/1'>Residues</scene> that interact with Leupeptin in the active site.  The predominant interaction is from hydrophobic interactions between Leupeptin and <scene name='Sandbox_31/1pophydrointeract/1'>active site residues</scene>.  In addition to hydrophobic interactions, there are also some hydrogen bonding interactions to hold Leupeptin in the active site of papain.  Leupeptin works well at blocking papain from its enzymatic duties.  A recent study has shown that Leupeptin actually forms a covalent bond between its <scene name='Sandbox_31/Leupeptin_active/1'>Carbonyl Carbon</scene> and CYS 25.  In addition, the residues Gln 19 and CYS 25 form <scene name='Sandbox_31/Leupeptin_active/2'>hydrogen bonds</scene> with the Leupeptin molecule
@@ Line 47: / Line 47: @@
 ===Clik-158===
-===Human Stefin B===
+'''Stefin B'''
+<scene name='Sandbox_36/Papain_inhibitor_space_fill/1'>Stefin B</scene> acts as a competitive inhibitor to cysteine proteases-- it binds tightly but reversibly to the papain active site.  Stefin inhibitors are characterized by M<sub>r</sub> of about 11,000, no disulfide bonds and no associated carbohydrates.
+In Stefin B, the Gly9 residue along with two hairpin loops form a "wedge" complementary to the active site groove of papain.  This wedge makes extensive and tight interactions with papain and a total of 128 intermolecular atom-atom interactions occur.  <scene name='Sandbox_36/Papain_inhibitor_wedge_involve/1'>Residue segments</scene> Met6-Pro11, Gln53-Asn59, Gln101-His104 and Tyr124-Phe125 on the wedge all have some interaction to the enzyme though not always direct.  All residues from the base and both sides of the <scene name='Sandbox_36/Papain_inhibitor_activ_involve/1'>active site cleft</scene> are involved in the complex with the inhibtor (Trp177, Ser21, Cys63, Cys25, Asp158 and His159).
+There are a small number of <scene name='Sandbox_36/Papain_inhibitor_direct_bond/2'>direct hydrogen bonds</scene> between stefin B and papain, however there are many more polar interactions mediated by <scene name='Sandbox_36/Papain_inhibitor_bridges_inter/1'>solvent bridges</scene>.  Thirteen solvent molecules bridge polar residues of the enzyme and inhibitor.  Seventeen hydrogen bonds are made with a solvent molecule and stefin.  Fourteen of these bridges form a papain contact.  The rest of the interactions are largely hydrophobic-- involving apolar <scene name='Sandbox_36/Papain_inhibitor_hydro_inter/2'>Van der Waals interactions</scene>. <ref> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC551902/pdf/emboj00233-0254.pdf </ref>