User:Michael Adams/Sandbox 1: Difference between revisions

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==Arginine Kinase==

A phosphokinase used to store energy in the form of Argininephosphate.

== ~~Discovery and~~ Isolation ==

== Isolation ==

In Strong and Ellington’s 1994 experiment, arginine kinase (AK) was isolated from Limulus polyphemus, the Atlantic horseshoe crab, a marine chelicerate arthropod. They isolated the gene for AK, sequenced the DNA and identified it to be 1071 nucleotides. The 1071 nucleotides produce a 357 amino acid protein and AK extracted from other organisms show similarity to this protein. AK serves a similar function to that of creatine kinase, in vertebrates <ref>Strong, S., & Ellington, W. (1994). Isolation and sequence analysis of the gene for

In Strong and Ellington’s 1994 experiment, arginine kinase (AK) was isolated from <i>Limulus polyphemus</i>, the Atlantic horseshoe crab, a marine chelicerate arthropod. They isolated the gene for AK, sequenced the DNA and identified it to be 1071 nucleotides. The 1071 nucleotides produce a 357 amino acid protein and AK extracted from other organisms show similarity to this protein. AK serves a similar function to that of creatine kinase, in vertebrates <ref>Strong, S., & Ellington, W. (1994). Isolation and sequence analysis of the gene for

arginine kinase from the chelicerate arthropod, Limulus polyphemus: Insights into

catalytically important residues. Biochimica Et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 197-200.</ref>. The enzyme creatine kinase maintains energy homeostasis by producing ATP in high energy requiring cells such as skeletal and cardiac muscle and neurons <ref name=wallimann1973>Wallimann, Theo, and Hans M. Eppenberger. "Properties of Arginine Kinase from

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Developmental Biology, Swiss Federal Institute of Technology, Zurich, 21 June 1973. Web. 12 Nov. 2015</ref>. This is done by the transfer of an N-phosphoryl group from phosphocreatine to ADP.

== Structure ==

The structure of arginine kinase is mainly α-helical and contains an N-terminal region with a specificity loop for specific substrate binding. (Figure 1b). However, when compared to creatine kinase, arginine kinase is not terminated at the N-terminal end with a pair of proline-glycine residues. Typically within creatine kinase, the proline molecules restrict changes in conformation and is the amino acid that terminates helices. The glycine chains are usually associated with flexibility. However, in arginine kinase this is typically not the case. On the C-terminal end, there is an eight-stranded antiparallel β-sheet with seven α-helices flanking the sheet (Figure 1).

The structure of <scene name='71/716599/My3/1'>arginine kinase</scene> is mainly α-helical and contains an N-terminal region with a specificity loop for specific substrate binding. (Figure 2). However, when compared to creatine kinase, arginine kinase is not terminated at the N-terminal end with a pair of proline-glycine residues. Typically within creatine kinase, the proline molecules restrict changes in conformation and is the amino acid that terminates helices. The glycine chains are usually associated with flexibility. However, in arginine kinase this is typically not the case. On the C-terminal end, there is an eight-stranded antiparallel <scene name='71/716599/Beta/1'>β-sheet</scene> with seven <scene name='71/716599/Mynewscene/1'>α-helices</scene> flanking the sheet (Figure 1). Residue <scene name='71/716599/330/2'>330</scene> is an arginine that appears to play a crucial role in maintaining structural stability. Studies show that a mutation in the residue leads to a steep decline in enzymatic activity <ref>DOI 10.1016/j.ijbiomac.2012.12.015</ref>.

[[Image:F1.large.jpg|frame|none|alt=Alt text|Figure 2. Structure of an ~~Arginine kinase~~ in ~~an unbound conformation]][[Image~~:~~3M10 bio r 500~~.jpg]]

~~Figure 1a (Left)~~. ~~Structure of an arginine kinase in substrate-bound form~~ Figure ~~1b (right)~~. Structure of an AK in an unbound conformation.

~~ATP + L-arginine ADP + Nω-phospho-L-arginine~~

The small domain specificity loop forms a “specificity” pocket surrounding the methyl substituent of the guanidinium group that is unique to creatine substrates. In this region, five residues differ between arginine and creatine kinases: 312, 314, 315, 317, and 319 <ref>Newsholme, E. A., Beis, I., Leech, A. R., & Zammit, V. A. (1978). The role of creatine

kinase and arginine kinase in muscle. Biochemical Journal, 172(3), 533–537.</ref>. Within each arginine kinase, there is typically a Mg+2 ion adjacent to the antiparallel β-sheet (Figure 1b). Typically two arginine kinase structures mirror each other and form a hole like structure in between the two~~. However, when a substrate is in the binding site, the active site remains unchanged and does not change in conformation~~ (Figure 1a).

kinase and arginine kinase in muscle. Biochemical Journal, 172(3), 533–537.</ref>. Within each arginine kinase, there is typically a Mg+2 ion adjacent to the antiparallel β-sheet (Figure 2) to aid in the increase of ATP’s affinity for the binding site <ref>DOI 10.1080/08927022.2011.561430</ref>. Typically two arginine kinase structures mirror each other and form a hole like structure in between the two (Figure 1).

== Function ==

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@@ Line 2: / Line 2: @@
 ==Arginine Kinase==
 A phosphokinase used to store energy in the form of Argininephosphate.
-== Discovery and Isolation ==
+== Isolation ==
-In Strong and Ellington’s 1994 experiment, arginine kinase (AK) was isolated from Limulus polyphemus, the Atlantic horseshoe crab, a marine chelicerate arthropod. They isolated the gene for AK, sequenced the DNA and identified it to be 1071 nucleotides. The 1071 nucleotides produce a 357 amino acid protein and AK extracted from other organisms show similarity to this protein. AK serves a similar function to that of creatine kinase, in vertebrates <ref>Strong, S., & Ellington, W. (1994). Isolation and sequence analysis of the gene for
+In Strong and Ellington’s 1994 experiment, arginine kinase (AK) was isolated from <i>Limulus polyphemus</i>, the Atlantic horseshoe crab, a marine chelicerate arthropod. They isolated the gene for AK, sequenced the DNA and identified it to be 1071 nucleotides. The 1071 nucleotides produce a 357 amino acid protein and AK extracted from other organisms show similarity to this protein. AK serves a similar function to that of creatine kinase, in vertebrates <ref>Strong, S., & Ellington, W. (1994). Isolation and sequence analysis of the gene for
 arginine kinase from the chelicerate arthropod, Limulus polyphemus: Insights into
 catalytically important residues. Biochimica Et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 197-200.</ref>. The enzyme creatine kinase maintains energy homeostasis by producing ATP in high energy requiring cells such as skeletal and cardiac muscle and neurons <ref name=wallimann1973>Wallimann, Theo, and Hans M. Eppenberger. "Properties of Arginine Kinase from
@@ Line 9: / Line 9: @@
 Developmental Biology, Swiss Federal Institute of Technology, Zurich, 21 June 1973. Web. 12 Nov. 2015</ref>. This is done by the transfer of an N-phosphoryl group from phosphocreatine to ADP.
 == Structure ==
-The structure of arginine kinase is mainly α-helical and contains an N-terminal region with a specificity loop for specific substrate binding.  (Figure 1b). However, when compared to creatine kinase, arginine kinase is not terminated at the N-terminal end with a pair of proline-glycine residues. Typically within creatine kinase, the proline molecules restrict changes in conformation and is the amino acid that terminates helices. The glycine chains are usually associated with flexibility. However, in arginine kinase this is typically not the case. On the C-terminal end, there is an eight-stranded antiparallel β-sheet with seven α-helices flanking the sheet (Figure 1).
+The structure of <scene name='71/716599/My3/1'>arginine kinase</scene> is mainly α-helical and contains an N-terminal region with a specificity loop for specific substrate binding.  (Figure 2). However, when compared to creatine kinase, arginine kinase is not terminated at the N-terminal end with a pair of proline-glycine residues. Typically within creatine kinase, the proline molecules restrict changes in conformation and is the amino acid that terminates helices. The glycine chains are usually associated with flexibility. However, in arginine kinase this is typically not the case. On the C-terminal end, there is an eight-stranded antiparallel <scene name='71/716599/Beta/1'>β-sheet</scene> with seven <scene name='71/716599/Mynewscene/1'>α-helices</scene> flanking the sheet (Figure 1). Residue <scene name='71/716599/330/2'>330</scene> is an arginine that appears to play a crucial role in maintaining structural stability. Studies show that a mutation in the residue leads to a steep decline in enzymatic activity <ref>DOI 10.1016/j.ijbiomac.2012.12.015</ref>.
-[[Image:F1.large.jpg|frame|none|alt=Alt text|Figure 2. Structure of an Arginine kinase in an unbound conformation]][[Image:3M10 bio r 500.jpg]]
+[[Image:F1.large.jpg|left|frame|none|alt=Alt text|Figure 1. Structure of an AK in substrate-bound form<ref>http://www.pnas.org/content/95/15/8449/F1.large.jpg</ref>]]
-Figure 1a (Left). Structure of an arginine kinase in substrate-bound form Figure 1b (right). Structure of an AK in an unbound conformation.
+[[Image:3M10 bio r 500.jpg|inline|left|frame|none|alt=Alt text|Figure 2. Structure of an AK in an unbound conformation<ref>http://www.rcsb.org/pdb/explore.do?structureId=4GVZ</ref>]]
-ATP + L-arginine  ADP + Nω-phospho-L-arginine
 The small domain specificity loop forms a “specificity” pocket surrounding the methyl substituent of the guanidinium group that is unique to creatine substrates.  In this region, five residues differ between arginine and creatine kinases: 312, 314, 315, 317, and 319 <ref>Newsholme, E. A., Beis, I., Leech, A. R., & Zammit, V. A. (1978). The role of creatine
-kinase and arginine kinase in muscle. Biochemical Journal, 172(3), 533–537.</ref>. Within each arginine kinase, there is typically a Mg+2 ion adjacent to the antiparallel β-sheet (Figure 1b). Typically two arginine kinase structures mirror each other and form a hole like structure in between the two.  However, when a substrate is in the binding site, the active site remains unchanged and does not change in conformation (Figure 1a).
+kinase and arginine kinase in muscle. Biochemical Journal, 172(3), 533–537.</ref>.  Within each arginine kinase, there is typically a Mg+2 ion adjacent to the antiparallel β-sheet (Figure 2) to aid in the increase of ATP’s affinity for the binding site <ref>DOI 10.1080/08927022.2011.561430</ref>. Typically two arginine kinase structures mirror each other and form a hole like structure in between the two (Figure 1).
 == Function ==