Sandbox 48
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| - | + | {{Template:Oberholser_Sandbox_Reservation}} | |
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| - | + | <Structure load='1ake' size='500' frame='true' align='right' caption='Adenylate Kinase' scene='Insert optional scene name here' /> | |
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| - | The <scene name='Sandbox_48/C-terminus_domain/2'>C-terminal domain</scene> is responsible for <scene name='Sandbox_48/Procolipase_with_lipase_contac/1'>binding</scene> to <scene name='Sandbox_48/Procolipase_with_lipase/1'>colipase</scene>, a small protein cofactor responsible for binding on to the inhibiting bile salt coated lipid-water interface. Without binding to colipase,lipase would not be able to catalyze the digestion of lipids because of the strong inhibitory effect of bile salts. This domain has a beta-sandwhich type morphology, made by four anti-parallel strands that allow for both hydrophobic and ionic binding of colipase. In the picture, lipase is complexed with pro-colipase, so no conformational change has been induced yet. With colipase, the flap covering the active site is moved to allow the binding of lipase to its substrate. This domain also has an active site that hydrolyzes ''p-nitrophenyl-acetate'' that is irreversibly acetylated on a lysine (Holmquist, 2000). | ||
| - | + | == Adenylate Kinase == | |
| - | Lipase can be complexed with <scene name='Sandbox_48/Lipase_w_inhibitor_c11_alkyl_p/2'>the inhibitor C11 alkyl phosphonate</scene> and have hydrogen bonded with <scene name='Sandbox_48/Lipase_w_inhibitor_c11_contact/1'>these residues</scene>. Here lipase is pictured with colipase and its covalent inhibitor, C11 alkyl phosphonate. It fits in a hydrophobic groove to mimic that of the true substrate of lipase, triglycerides. Some are trying to find drugs that inhibit lipase in order to combat obesity. Although this inhibitor is not necessarily a candidate, its structure has aided researchers in developing a true inhibitor. | ||
| + | <scene name='Sandbox_48/Full_adenylate_kinase/1'>Adenylate kinase</scene> (or ADK) is an enzyme known to catalyze the reversible interconversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to two molecules of adenosine diphosphate (ADP). | ||
| + | Reaction Scheme: ATP + AMP ⇔ 2 ADP | ||
| + | This enzyme is important for cellular energy homeostasis because the need for ADP. ADP is required for oxidative phosphorylation, an important step in multiple metabolic pathways. | ||
| - | == | + | == Secondary Structure & Hydrogen Bonds == |
| - | + | The structure of <scene name='Sandbox_48/Adenylate_kinase__chain_a/1'>chain A in adenylate kinase</scene> demonstrates the types of secondary structure that make up the enzyme. | |
| - | + | The <scene name='Sandbox_48/Secondary__structure__greenblu/4'>secondary structures</scene> of chain A of adenylate kinase includes alpha- | |
| + | <scene name='Sandbox_48/Secondary__structure__helix/1'>helices</scene> (green), and <scene name='Sandbox_48/Secondary__structure__betashee/1'>beta sheets</scene> (blue). There are 12 total helices in the enzyme, and 2 types of | ||
| + | beta sheets, a parallel with 5 strands and an antiparallel with 2 strands. The location of the <scene name='Sandbox_48/2_structure_hbondson/1'>hydrogen bonds</scene> (black) within the secondary structure demonstrates how the alpha-helices and beta-sheets are hydrogen bonded. | ||
| - | + | == Hydrophobic and Hydrophilic Residues == | |
| - | </ | + | Within these structures the <scene name='Sandbox_48/Secondary__structure__hydropho/1'>hydrophobic</scene> residues (purple) are located closest on the inside of the enzyme. The <scene name='Sandbox_48/Secondary__structure__hydrophi/1'>hydrophillic </scene> residues (green), which are those that are charged or polar, are on the outward face of the enzyme. |
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| + | == Solvent Accessibility == | ||
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| + | In the presence of <scene name='Sandbox_48/Chain_a__w__waterligand/1'>solvent</scene>, the polar, hydrophilic residues of adenylate kinase interact with the molecules of solvent (purple). There is also solvent accessibility near the center of the molecule at the active site, and it is also accessible on the outward chains like the alpha helices. The ligand (green) is highlighted to show that the water molecules surround the ligand in the middle of the ligand, but not by the ends. | ||
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| + | == Ligand Interaction == | ||
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| + | There are charged residues that <scene name='Sandbox_48/Ligand__interaction__charges/1'>interact with the ligand</scene>, or make up the interaction site. The positively charged (blue) residues of the enzyme, which would include arginine (R123, R156, R167) and lysine (K13) interact with the negatively charged (red) residues of the ligand. There are also negatively charged portions of the active site, such as aspartic acid (D158, D159) that will interact with positively charged residues of the ligand. | ||
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| + | The <scene name='Sandbox_48/Adenylate_kinase_ligand/1'>ligand</scene> pictured is the inhibitory, non-hydrolyzable version of a substrate. It is similar in structure to ATP, but at the end of the triphosphate there is another adenosine. This will stop the reaction, and will allow our enzyme's structure to be analyzed in presence of a substrate. | ||
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. |
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Contents |
Adenylate Kinase
(or ADK) is an enzyme known to catalyze the reversible interconversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to two molecules of adenosine diphosphate (ADP).
Reaction Scheme: ATP + AMP ⇔ 2 ADP
This enzyme is important for cellular energy homeostasis because the need for ADP. ADP is required for oxidative phosphorylation, an important step in multiple metabolic pathways.
Secondary Structure & Hydrogen Bonds
The structure of demonstrates the types of secondary structure that make up the enzyme.
The of chain A of adenylate kinase includes alpha- (green), and (blue). There are 12 total helices in the enzyme, and 2 types of beta sheets, a parallel with 5 strands and an antiparallel with 2 strands. The location of the (black) within the secondary structure demonstrates how the alpha-helices and beta-sheets are hydrogen bonded.
Hydrophobic and Hydrophilic Residues
Within these structures the residues (purple) are located closest on the inside of the enzyme. The residues (green), which are those that are charged or polar, are on the outward face of the enzyme.
Solvent Accessibility
In the presence of , the polar, hydrophilic residues of adenylate kinase interact with the molecules of solvent (purple). There is also solvent accessibility near the center of the molecule at the active site, and it is also accessible on the outward chains like the alpha helices. The ligand (green) is highlighted to show that the water molecules surround the ligand in the middle of the ligand, but not by the ends.
Ligand Interaction
There are charged residues that , or make up the interaction site. The positively charged (blue) residues of the enzyme, which would include arginine (R123, R156, R167) and lysine (K13) interact with the negatively charged (red) residues of the ligand. There are also negatively charged portions of the active site, such as aspartic acid (D158, D159) that will interact with positively charged residues of the ligand.
The pictured is the inhibitory, non-hydrolyzable version of a substrate. It is similar in structure to ATP, but at the end of the triphosphate there is another adenosine. This will stop the reaction, and will allow our enzyme's structure to be analyzed in presence of a substrate.
