Sandbox Reserved 763: Difference between revisions

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Magnesium ions bind in the active site and hold influence over the position of shikimate hydroxy groups. This ion has a role in the transfer of the γ-phosphate of ATP to the 3-hydroxy group on shikimate. Chloride ions increase enzyme affinity for ADP and ATP and help to bind the nucleotide substrate in correct orientation.<ref name="mgcl"> Effects of the magnesium and chloride ions and shikimate on the structure of shikimate kinase from Mycobacterium tuberculosis Structural Biology and Crystallization Communications

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330112/</ref> Sulfate is replaced with MgATP in the ternary complex of SK to allow for the reaction to occur.<ref name="sulfate"> Mechanism of Phosphoryl Transfer Catalyzed by Shikimate Kinase from Mycobacterium tuberculosis. Journal of Molecular Biology. http://www.sciencedirect.com/science/article/pii/S0022283606011685 </ref> Sulfate interacts with Arg117 and distorts the nucleotide binding site<ref name="miscinfo" />

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330112/</ref> Sulfate is replaced with MgATP in the ternary complex of SK to allow for the reaction to occur.<ref name="sulfate"> Mechanism of Phosphoryl Transfer Catalyzed by Shikimate Kinase from Mycobacterium tuberculosis. Journal of Molecular Biology. http://www.sciencedirect.com/science/article/pii/S0022283606011685 </ref> Sulfate interacts with Arg117 and distorts the nucleotide binding site<ref name="miscinfo" /> Sulfate binds and distorts the nucleotide binding site, leading to a large decrease of motion.<ref name="miscinfo" />

===Inhibitors===

~~When sulfate binds as a ligand, it distorts~~ the nucleotide binding site. This leads to a large decrease of motion in comparison to a nucleotide binding. The implication of this is that Ser16OG and Asp32OD2 are no longer close enough to hydrogen bond and bring about contact between the CORE and SB domains.<ref name="miscinfo" /> This may not strictly fall under the definition of an inhibitor, but is still worth noting.

See the section on [[#Implications or Possible Applications|Implications or Possible Applications]]

==Implications or Possible Applications==

~~Describe how protein functions. Structures of Ligands/inhibitors/important steps in reaction pathway.~~

==Implications or Possible ~~Application~~==

Enzymes present in the shikimate pathway are important in microorganism survival yet absent in mammals. This means the enzymes of the SKM pathway are good candidates for antimicrobial agents, herbicides, inhibitors, and anti-parasitic drug target.

<ref name="miscinfo" /><ref name="inhibitors"> Identification of new potential Mycobacterium tuberculosis shikimate kinase inhibitors through molecular docking simulations. Journal of Molecular Modeling http://link.springer.com.prox.lib.ncsu.edu/article/10.1007%2Fs00894-011-1113-5

Sandbox Reserved 763: Difference between revisions

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@@ Line 173: / Line 173: @@
 Magnesium ions bind in the active site and hold influence over the position of shikimate hydroxy groups. This ion has a role in the transfer of the γ-phosphate of ATP to the 3-hydroxy group on shikimate. Chloride ions increase enzyme affinity for ADP and ATP and help to bind the nucleotide substrate in correct orientation.<ref name="mgcl"> Effects of the magnesium and chloride ions and shikimate on the structure of shikimate kinase from Mycobacterium tuberculosis Structural Biology and Crystallization Communications
-http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330112/</ref> Sulfate is replaced with MgATP in the ternary complex of SK to allow for the reaction to occur.<ref name="sulfate"> Mechanism of Phosphoryl Transfer Catalyzed by Shikimate Kinase from Mycobacterium tuberculosis. Journal of Molecular Biology. http://www.sciencedirect.com/science/article/pii/S0022283606011685 </ref> Sulfate interacts with Arg117 and distorts the nucleotide binding site<ref name="miscinfo" />
+http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330112/</ref> Sulfate is replaced with MgATP in the ternary complex of SK to allow for the reaction to occur.<ref name="sulfate"> Mechanism of Phosphoryl Transfer Catalyzed by Shikimate Kinase from Mycobacterium tuberculosis. Journal of Molecular Biology. http://www.sciencedirect.com/science/article/pii/S0022283606011685 </ref> Sulfate interacts with Arg117 and distorts the nucleotide binding site<ref name="miscinfo" /> Sulfate binds and distorts the nucleotide binding site, leading to a large decrease of motion.<ref name="miscinfo" />
 ===Inhibitors===
-When sulfate binds as a ligand, it distorts the nucleotide binding site. This leads to a large decrease of motion in comparison to a nucleotide binding. The implication of this is that Ser16OG and Asp32OD2 are no longer close enough to hydrogen bond and bring about contact between the CORE and SB domains.<ref name="miscinfo" /> This may not strictly fall under the definition of an inhibitor, but is still worth noting.
+See the section on [[#Implications or Possible Applications|Implications or Possible Applications]]
+==Implications or Possible Applications==
-Describe how protein functions. Structures of Ligands/inhibitors/important steps in reaction pathway.
-==Implications or Possible Application==
 Enzymes present in the shikimate pathway are important in microorganism survival yet absent in mammals. This means the enzymes of the SKM pathway are good candidates for antimicrobial agents, herbicides, inhibitors, and anti-parasitic drug target.
 <ref name="miscinfo" /><ref name="inhibitors"> Identification of new potential Mycobacterium tuberculosis shikimate kinase inhibitors through molecular docking simulations. Journal of Molecular Modeling http://link.springer.com.prox.lib.ncsu.edu/article/10.1007%2Fs00894-011-1113-5