User:Michael Roberts/BIOL115 Chymo: Difference between revisions
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[[Image:Chymo.png|left|150px|thumb|Chymotrypsin active site, [[1aqf]]]] | |||
<span style="font-size:150%">'''Chymotrypsin.'''</span> | <span style="font-size:150%">'''Chymotrypsin.'''</span> | ||
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Click on the ''' 'green links' ''' in the text in the scrollable section below to examine this molecule in more detail. | Click on the ''' 'green links' ''' in the text in the scrollable section below to examine this molecule in more detail. | ||
<StructureSection load='1afq' size='500' side='right' caption='Structure of | <StructureSection load='1afq' size='500' side='right' caption='Structure of bovine chymotrypsin (PDB entry [[1afq]])' scene='User:Michael_Roberts/BIOL115_Chymo/Start/1'> | ||
== Tertiary structure == | == Tertiary structure == | ||
Chymotrypsin is initially synthesized as a 245 amino acid inactive precursor (a zymogen) termed chymotrypsinogen. Activation of chymotrypsinogen involves proteolytic cleavage at two sites along the chain and removal of two amino acids at each cleavage site. The resultant <scene name='User:Michael_Roberts/BIOL115_Chymo/Chains/1'>three chains</scene> are shown here (chain 1 = 1-13 in green; chain 2 = 16-146 in red; chain 3 = 149-24 in blue). Note, some amino acids at the temini of these chains are not shown in this representation (e.g. 11-13, 149, ). This is because these residues show too much flexibility in the crystal structures to give X-ray diffraction patterns which would locate them in space. | Chymotrypsin is initially synthesized as a 245 amino acid inactive precursor (a zymogen) termed chymotrypsinogen. Activation of chymotrypsinogen involves proteolytic cleavage at two sites along the chain and removal of two amino acids at each cleavage site. The resultant <scene name='User:Michael_Roberts/BIOL115_Chymo/Chains/1'>three chains</scene> are shown here (chain 1 = 1-13 in green; chain 2 = 16-146 in red; chain 3 = 149-24 in blue). Note, some amino acids at the temini of these chains are not shown in this representation (e.g. 11-13, 149, ). This is because these residues show too much flexibility in the crystal structures to give X-ray diffraction patterns which would locate them in space. | ||
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The <scene name='User:Michael_Roberts/BIOL115_Chymo/2ndry_structure/3'>active site</scene> of chymotrypsin consists of Asp102 positioned close to His 57 and Ser 195. The precise mechanism of action is still debated, but it appears that a hydrogen on the his imidazole ring is transferred to the Asp 102 carboxylate (either via a "charge relay system" or via a "low barrier H-bond"). This shift results in the histidine ring being able to accept the serine 195 hydroxyl hydrogen, forming a very nucleophilic serine alkoxide ion. | The <scene name='User:Michael_Roberts/BIOL115_Chymo/2ndry_structure/3'>active site</scene> of chymotrypsin consists of Asp102 positioned close to His 57 and Ser 195. The precise mechanism of action is still debated, but it appears that a hydrogen on the his imidazole ring is transferred to the Asp 102 carboxylate (either via a "charge relay system" or via a "low barrier H-bond"). This shift results in the histidine ring being able to accept the serine 195 hydroxyl hydrogen, forming a very nucleophilic serine alkoxide ion. | ||
'''Binding of the Substrate''' | '''Binding of the Substrate''' | ||
This structure contains a competitive inhibitor, <scene name='User:Michael_Roberts/BIOL115_Chymo/Substrate/1'>D-leucyl-L-phenylalanyl-p-fluorobenzylamide</scene>. This is a dipeptide of Leu and Phe (orange), plus a fluorobenzylamide group (red), which is aromatic and bound in the specificity pocket (see next button). In an actual substrate, the peptide bond cleaved would be to the carboxyl side of the aromatic amino acid. In this inhibitor, there are two residues to the amide side, but there is no residue to what would be the carboxyl side. Thus, there is no cleavable bond in this structure. | This structure contains a competitive inhibitor, <scene name='User:Michael_Roberts/BIOL115_Chymo/Substrate/1'>D-leucyl-L-phenylalanyl-p-fluorobenzylamide</scene>. This is a dipeptide of Leu and Phe (orange), plus a fluorobenzylamide group (red), which is aromatic and bound in the specificity pocket (see next button). In an actual substrate, the peptide bond cleaved would be to the carboxyl side of the aromatic amino acid. In this inhibitor, there are two residues to the amide side, but there is no residue to what would be the carboxyl side. Thus, there is no cleavable bond in this structure. | ||
'''The Active Site Environment''' | '''The Active Site Environment''' | ||