Sandbox 50: Difference between revisions

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==Ion Contacts==

Trypsin interacts with four <scene name='Sandbox_50/Ioncontact/2'>ions</scene>. The red and yellow atoms are the ions. The yellow atoms are sulfur and the red atoms are oxygen.

=Catalytic Mechanism=

==Catalytic Mechanism==

[[Image:Serine_protease_mechanism_by_snellios.png |thumb]]

==Active Site==

===Active Site===

Trypsin's active site is composed of its catalytic triad, three amino acid residues that are crucial to the enzymes proteolytic function. The catalytic triad consists of Asp 102, His 57, and Ser 195. Serine is the major player in the cleaveage of the peptide bond, thus the name serine protease. His 57 and Asp 102 ~~aid~~ in the cleavage by ~~hydrogen bonding and~~ electrostatically stabalizing the ~~substrate~~. Ser 195 performs a nucleophilic attack on the substrate's peptide carbonyl. This causes the oxyanion hole to form. The nucleophilic attack by the oxygen of Ser 195 also forms a tetrahedral intermediate. By reconstruction of the carbonyl double bound, the amino portion of the peptide leaves as a product, and an acyl-enzyme intermediate is left in the active site. Now the active site needs to be regenerated. To do this a water molecule nucleophillically attacks the carbonyl carbon, forming another tetrahedral intermediate and reforming the oxyanion hole. The nitrogen of the His 57 ring makes the oxygen of the water more nucleophilic by hydrogen bonding to one of water's hydrogens. By reforming the double bond of the carbonyl carbon, the carboxy end of the original substrate's peptide bond is released, and the active site has been regenerated. The picture in the thumbnail to the left shows the entire catalytic mechanism for a serine protease. A figure of the oxyanion hole can be seen in greater detail in the thumbnail on the left.

Trypsin's active site is composed of its catalytic triad, three amino acid residues that are crucial to the enzymes proteolytic function. The catalytic triad consists of Asp 102, His 57, and Ser 195. Serine is the major player in the cleaveage of the peptide bond, thus the name serine protease. His 57 aids in the cleavage of the peptide bond through hydrogen bonds, and Asp 102 aids in the cleavage by electrostatically stabalizing the positively charged form of His 57 in the transition state. Ser 195 performs a nucleophilic attack on the substrate's peptide carbonyl. This causes the oxyanion hole to form. The nucleophilic attack by the oxygen of Ser 195 also forms a tetrahedral intermediate. By reconstruction of the carbonyl double bound, the amino portion of the peptide leaves as a product, and an acyl-enzyme intermediate is left in the active site. Now the active site needs to be regenerated. To do this a water molecule nucleophillically attacks the carbonyl carbon, forming another tetrahedral intermediate and reforming the oxyanion hole. The nitrogen of the His 57 ring makes the oxygen of the water more nucleophilic by hydrogen bonding to one of water's hydrogens. By reforming the double bond of the carbonyl carbon, the carboxy end of the original substrate's peptide bond is released, and the active site has been regenerated. The picture in the thumbnail to the left shows the entire catalytic mechanism for a serine protease. A figure of the oxyanion hole can be seen in greater detail in the thumbnail on the left.

[[Image:Triad 1.jpg |thumb]]

==Zymogen: Trypsin Precursor==

===Trypsinogen===

A zymogen is an inactive enzyme precursor. Trypsinogen is the zymogen of Trypsin that is secreted by the pancreas and is converted into the active form Trypsin in the duodenum of the small intestine. It is converted into Trypsin by proteolysis. Trypsin needs to be synthesized and secreted in an inactive form to prevent unwanted destruction of other cellular proteins, and also to regulare when and where enzyme activity of Trypsin can occur.

In order for trypsinogen to be converted to trypsin, a pro-peptide must be cleaved from trypsinogen. The image at the left shows which sequence is removed from trypsinogen, and the active site of trypsin becomes accessible for its protein substrate.

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@@ Line 16: / Line 16: @@
 ==Ion Contacts==
 Trypsin interacts with four <scene name='Sandbox_50/Ioncontact/2'>ions</scene>. The red and yellow atoms are the ions. The yellow atoms are sulfur and the red atoms are oxygen.
-=Catalytic Mechanism=
+==Catalytic Mechanism==
 [[Image:Serine_protease_mechanism_by_snellios.png |thumb]]
-==Active Site==
+===Active Site===
-Trypsin's active site is composed of its catalytic triad, three amino acid residues that are crucial to the enzymes proteolytic function. The catalytic triad consists of Asp 102, His 57, and Ser 195. Serine is the major player in the cleaveage of the peptide bond, thus the name serine protease. His 57 and Asp 102 aid in the cleavage by hydrogen bonding and electrostatically stabalizing the substrate. Ser 195 performs a nucleophilic attack on the substrate's peptide carbonyl. This causes the oxyanion hole to form. The nucleophilic attack by the oxygen of Ser 195 also forms a tetrahedral intermediate. By reconstruction of the carbonyl double bound, the amino portion of the peptide leaves as a product, and an acyl-enzyme intermediate is left in the active site. Now the active site needs to be regenerated. To do this a water molecule nucleophillically attacks the carbonyl carbon, forming another tetrahedral intermediate and reforming the oxyanion hole. The nitrogen of the His 57 ring makes the oxygen of the water more nucleophilic by hydrogen bonding to one of water's hydrogens. By reforming the double bond of the carbonyl carbon, the carboxy end of the original substrate's peptide bond is released, and the active site has been regenerated. The picture in the thumbnail to the left shows the entire catalytic mechanism for a serine protease. A figure of the oxyanion hole can be seen in greater detail in the thumbnail on the left.
+Trypsin's active site is composed of its catalytic triad, three amino acid residues that are crucial to the enzymes proteolytic function. The catalytic triad consists of Asp 102, His 57, and Ser 195. Serine is the major player in the cleaveage of the peptide bond, thus the name serine protease. His 57 aids in the cleavage of the peptide bond through hydrogen bonds, and Asp 102 aids in the cleavage by electrostatically stabalizing the positively charged form of His 57 in the transition state. Ser 195 performs a nucleophilic attack on the substrate's peptide carbonyl. This causes the oxyanion hole to form. The nucleophilic attack by the oxygen of Ser 195 also forms a tetrahedral intermediate. By reconstruction of the carbonyl double bound, the amino portion of the peptide leaves as a product, and an acyl-enzyme intermediate is left in the active site. Now the active site needs to be regenerated. To do this a water molecule nucleophillically attacks the carbonyl carbon, forming another tetrahedral intermediate and reforming the oxyanion hole. The nitrogen of the His 57 ring makes the oxygen of the water more nucleophilic by hydrogen bonding to one of water's hydrogens. By reforming the double bond of the carbonyl carbon, the carboxy end of the original substrate's peptide bond is released, and the active site has been regenerated. The picture in the thumbnail to the left shows the entire catalytic mechanism for a serine protease. A figure of the oxyanion hole can be seen in greater detail in the thumbnail on the left.
 [[Image:Triad 1.jpg |thumb]]
+==Zymogen: Trypsin Precursor==
+===Trypsinogen===
+A zymogen is an inactive enzyme precursor. Trypsinogen is the zymogen of Trypsin that is secreted by the pancreas and is converted into the active form Trypsin in the duodenum of the small intestine. It is converted into Trypsin by proteolysis. Trypsin needs to be synthesized and secreted in an inactive form to prevent unwanted destruction of other cellular proteins, and also to regulare when and where enzyme activity of Trypsin can occur.
+In order for trypsinogen to be converted to trypsin, a pro-peptide must be cleaved from trypsinogen. The image at the left shows which sequence is removed from trypsinogen, and the active site of trypsin becomes accessible for its protein substrate.