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| - | <applet load='1QLQ' size='300' frame='true' align='right' caption='Trypsin' /> | + | <!-- PLEASE DO NOT DELETE THIS TEMPLATE --> |
| | + | {{Template:Oberholser_Sandbox_Reservation}} |
| | + | <!-- PLEASE ADD YOUR CONTENT BELOW HERE --> |
| | + | <Structure load='1AKE A' size='500' frame='true' align='right' caption='Adenylate Kinase' scene='Sandbox_46/1ake_main/2' /> |
| | + | =Adenylate Kinase= |
| | + | <scene name='Sandbox_46/1ake_main/2'>Adenylate kinase</scene> is a enzyme that catalyzes the conversion of 2 units of ADP into a unit of ATP and a unit of AMP. It is because of this catalytic role that adenylate kinase is an important part of homeostasis. Consisting of only 211 amino acids, adenylate kinase is not that large of an enzyme, despite its vital role in metabolism. |
| | + | =Structure= |
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| - | =Trypsin= | + | The <scene name='Sandbox_46/1ake_secondary/1'>secondary structure</scene> of adenylate kinase shows alpha helices (blue) and beta sheets (teal) surrounding the non-hydrolysable substrate analogue. The enzyme is comprised of 9 helices and 9 sheets constituting the secondary structure. As with any enzyme, the <scene name='Sandbox_46/1ake_hydrogen/1'>hydrogen bonds</scene> (May not load) between the residues of the peptide chains supply the final folded protein with structural stability which helps hold it in its folded configuration. |
| - | Trypsin, a member of the serine protease family, is produced in the pancreas and found in the digestive tracks of vertebrates. To avoid pancreatic self-degradation, trypsin is synthesized as trypsinogen, a zymogen. Cleavage by enteropeptidase allows tryspin to enter its active form. As a serine protease, trypsin contains a serine residue in its active site.<ref name="pmid7845208">"Trypsin." Wikipedia, the Free Encyclopedia. Web. 30 Oct. 2010. <http://en.wikipedia.org/wiki/Trypsin#Structure_and_function>.</ref>
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| | + | This secondary structure is oriented as such so that the <scene name='Sandbox_46/1ake_phobicphilic/2'>hydrophobic and hydrophilic residues</scene> are buried or exposed depending on their individual properties. The hydrophobic, represented in grey, are buried as to avoid as much contact with water as possible. Similarly, the hydrophilic, or polar, residues are colored purple and exposed as much to water as possible. This is further illustrated by the <scene name='Sandbox_46/1ake_water/1'>water solvation</scene> model, displaying water molecules as pink orbs and the enzyme as a translucent white. These hydrophobic interactions, burying of non polar residues and exposure of polar ones, is another main driving force conserving the tertiary structure of the enzyme. |
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| - | ==Structure==
| + | The model of adenylate kinases shows displays the non-hydrolysable substrate as the ligand. The <scene name='Sandbox_46/1ake_ligandinteract/1'>residues interacting with the ligand</scene> are polar as the substrate is also highly negatively charged. The ligand can be seen in the active site of the enzyme, and shown in standard atomic coloring scheme. The <scene name='Sandbox_46/1ake_catalytic/1'>catalytic residues</scene> are the residues that directly interact with the ligand, and can be seen in yellow. |
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| - | The trypsin structure displayed is a mutant form isolated from a bovine pancreas. It contains 58 amino acid residues as well as an altered binding loop. To follow the primary structure (amino acid sequence) of Trypsin, click <scene name='Sandbox_46/Secondary_structure_tryp/2'>here.</scene> Begin at the N-terminus (blue) and move toward the C-terminus (red). | + | |
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| - | The <scene name='Sandbox_46/Tryp_secondary_color/2'>secondary structure</scene> of Trypsin consists of two alpha helices (light green) and two beta sheets (peach). | + | |
| - | Hydrophobic interactions - mainly the hydrophobic collapse - significantly contribute to both secondary and tertiary structure. This <scene name='Sandbox_46/Polar_vs_nonpolar_wire/1'>structure</scene> shows that the majority of the residues are non-polar/hydrophobic (maroon). These residues tend to congregate on the interior of the structure while polar/hydrophilic residues (blue) remain on the exterior. This orientation allows polar molecules to maximize interaction with water and other polar molecules while non-polar molecules minimize such interactions. Adding water molecules to the model, the <scene name='Sandbox_46/Polar_vs_nonpolar/1'>polar/non-polar</scene> interactions can be seen. The color configuration remains with water molecules displayed in green.
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| - | ===Stability===
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| - | Many factors contribute to protein stabilization. Disulphide bonds form between the Sulfur atoms of two Cysteine residues and assist in the formation of the tertiary structure. This particular form of trypsin contains three <scene name='Sandbox_46/Disulfide_bonds/3'>disulphide bonds</scene> (yellow). These bonds interact between Cysteine residues at positions 5 and 55, 14 and 38, 30 and 51. Disulphide bond two (residues 14 and 38) interacts with two chiral centers; thus, one Sulfur atom interacts with two Sulfur atoms opposite it. Click <scene name='Sandbox_46/Disulfide_bonds_123/1'>here</scene> to see the labeled disulphide bonds.
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| - | In addition to disulphide bonds, Hydrogen bonding plays a large role in stability. As this <scene name='Sandbox_46/Hbonds_backbone/1'>model</scene> suggests, hydrogen bonds (orange) are most prominent in alpha helices and beta sheets of the backbone. In alpha helices, hydrogen bonds form between an H-N and a C-O 4 residue away; complementing the specific turn length (3.6 residues). Hydrogen bonds between the <scene name='Sandbox_46/H_bonds_r_groups/1'>sidechain residues</scene> (R groups) provide further stability for the trypsin moiety.
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| - | The yellow and red molecules represent <scene name='Sandbox_46/So4/1'>SO4 (2-) molecules</scene> which are not part of the traditional trypsin structure; they were added during crystallization to freeze Trypsin in a specific conformation. Each SO4 molecule is bound to an active site (ball and stick display) in order to prevent interaction with another substrate. <ref>Czapinska, H., J. Otlewski, S. Krzywda, G. M. Sheldrick, and M. Jaskolski. "RCSB Protein Data Bank - Structure Summary for 1QLQ - BOVINE PANCREATIC TRYPSIN INHIBITOR (BPTI) MUTANT WITH ALTERED BINDING LOOP SEQUENCE." Http://www.rcsb.org/pdb/explore/explore.do?structureId=1QLQ. (1999) J.Mol.Biol. 295: 1237. Web. 30 Oct. 2010. <http://www.rcsb.org/pdb/explore.do?structureId=1qlq>.</ref> Active site inhibition is a prominent method for studying enzymes.
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| - | ==Function==
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| - | Enteropeptidase cleaves after Lysine if it is preceded by 4 Aspartic Acid residues and not followed by a Proline residue. <ref>"Enteropeptidase." Wikipedia, the Free Encyclopedia. Web. 30 Oct. 2010. <http://en.wikipedia.org/wiki/Enteropeptidase>.</ref> This particular cleavage converts trypsinogen (zymogen) into trypsin.
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| - | Once activated, trypsin catalyzes the hydrolysis of peptides into amino acids which the body can absorb during digestion. Trypsin has an affinity for positively charged molecules; thus, it specifically cleaves on the carboxyl end (after) of Lysine and Arginine, unless Proline follows the residue. Trypsin's active site normally contains a triad of residues: Histidine, Serine, and Apartic Acid. <ref name="pmid7845208">"Trypsin." Wikipedia, the Free Encyclopedia. Web. 30 Oct. 2010. <http://en.wikipedia.org/wiki/Trypsin#Structure_and_function>.</ref> The particular mutant form discussed here does not contain this particular active site, but rather 4 different active sites. Click on any of the following links to view a specific active site: <scene name='Sandbox_46/Ac1/1'>Active Site 1</scene> (light blue); <scene name='Sandbox_46/Ac2/1'>Active Site 2</scene> (pink); <scene name='Sandbox_46/Ac3/1'>Active Site 3</scene>(yellow); <scene name='Sandbox_46/Ac4/1'>Active Site 4</scene> (dark blue). This <scene name='Sandbox_46/Ac_all/1'>model</scene> compares the orientation of all four active sites. Site 1 and 3 share a small portion (Arginine residue 42) which is shown in maroon. Active site three most closely resembles the traditional composition of trypsin's active site.
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| - | ==References==
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| - | {{Reflist}}
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Current revision
| Please do NOT make changes to this Sandbox. Sandboxes 30-60 are reserved for use by Biochemistry 410 & 412 at Messiah College taught by Dr. Hannah Tims during Fall 2012 and Spring 2013. |
Adenylate Kinase
is a enzyme that catalyzes the conversion of 2 units of ADP into a unit of ATP and a unit of AMP. It is because of this catalytic role that adenylate kinase is an important part of homeostasis. Consisting of only 211 amino acids, adenylate kinase is not that large of an enzyme, despite its vital role in metabolism.
Structure
The of adenylate kinase shows alpha helices (blue) and beta sheets (teal) surrounding the non-hydrolysable substrate analogue. The enzyme is comprised of 9 helices and 9 sheets constituting the secondary structure. As with any enzyme, the (May not load) between the residues of the peptide chains supply the final folded protein with structural stability which helps hold it in its folded configuration.
This secondary structure is oriented as such so that the are buried or exposed depending on their individual properties. The hydrophobic, represented in grey, are buried as to avoid as much contact with water as possible. Similarly, the hydrophilic, or polar, residues are colored purple and exposed as much to water as possible. This is further illustrated by the model, displaying water molecules as pink orbs and the enzyme as a translucent white. These hydrophobic interactions, burying of non polar residues and exposure of polar ones, is another main driving force conserving the tertiary structure of the enzyme.
The model of adenylate kinases shows displays the non-hydrolysable substrate as the ligand. The are polar as the substrate is also highly negatively charged. The ligand can be seen in the active site of the enzyme, and shown in standard atomic coloring scheme. The are the residues that directly interact with the ligand, and can be seen in yellow.
