Sandbox 48

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(Adenylate Kinase)
 
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{{Template:Tims Sandbox Reservation}} <applet load='3iju' size='300' frame='true' align='right' caption='Hen Egg White Lysozyme' />
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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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== General Preliminary Information and Historical Development ==
 
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Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. In avian species, lysozyme is an abundant component of egg white, in which lysozyme functions as an antibiotic and as a nutrient for early embryogenesis <ref>Sears, D.W. 2010. Overview of the Structure and Function of Hen Egg-White Lysozyme. Ucsb.edu. http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm/</ref>. In vertebrate species, lysozyme is generally found in mucosal secretions, such as tears and saliva, and functions in the same way that it functions in avian species for antibacterial purposes.
 
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The discovery of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since, by successfully elucidating the structure of lysozyme via X-ray crystallography, Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the historical development of the understanding of the structure and function of lysozyme has been paramount to the more general realm of enzyme chemistry.
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== Adenylate Kinase ==
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== General Function ==
 
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Lysozyme is a 129 amino acid-long enzyme that is particularly specific in its cleavage proclivity for alternating polysaccharide copolymers of N-acetyl glucosamine (NAG) and N-acetyl muramic acid (NAM), which architectural theme represents the "unit" polysaccharide structure of many bacterial cell walls <ref>Sears, D.W. 2010. Overview of the Structure and Function of Hen Egg-White Lysozyme. Ucsb.edu. http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm/</ref>. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting connecting the C1 carbon of NAM to the C4 carbon of NAG. The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the cleaving target glycosidic bond of NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with the NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.
 
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<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).
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<references/>
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Reaction Scheme: ATP + AMP ⇔ 2 ADP
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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.
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== Secondary Structure & Hydrogen Bonds ==
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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.
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The <scene name='Sandbox_48/Secondary__structure__greenblu/4'>secondary structures</scene> of chain A of adenylate kinase includes alpha-
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<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
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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.
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== Hydrophobic and Hydrophilic Residues ==
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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.

Adenylate Kinase

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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.

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