Sandbox Reserved 763: Difference between revisions
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Shikimate kinase is an enzyme which participates in the fifth step of the shikimate pathway. The functional role shikimate kinase plays in this pathway is to catalyze the ATP-dependent phosphorylation of shikimate into shikimate 3-phosphate (3-phosphoshikimate). This aids in the synthesis of chorismate, which is the precursor to aromatic amino acids and secondary metabolites. Shikimate kinase is a protein kinase, an enzyme which phosphorylates a protein leading to a functional change in the phosphorylated protein, of the transferase class. A transferase acts to transfer a functional group from the donor to acceptor molecule. The protein fold consists of 9 helices | Shikimate kinase is an enzyme which participates in the fifth step of the shikimate pathway. The functional role shikimate kinase plays in this pathway is to catalyze the ATP-dependent phosphorylation of shikimate into shikimate 3-phosphate (3-phosphoshikimate). This aids in the synthesis of chorismate, which is the precursor to aromatic amino acids and secondary metabolites. Shikimate kinase is a protein kinase, an enzyme which phosphorylates a protein leading to a functional change in the phosphorylated protein, of the transferase class. A transferase acts to transfer a functional group from the donor to acceptor molecule. The protein fold consists of 9 helices and 5 strands. The length of shikimate kinase ranges from 161-214 residues and it is found in the cytoplasm. This is a subclass of alpha/beta proteins, meaning an alpha/beta domain exists. The subunit is that of a monomer. This enzyme consists of the CORE, LED, and substrate-binding domains. ATP is the cosubstrate while magnesium ion is the cofactor. Though the shikimate pathway is present in microorganisms and plants, shikimate kinase is found only in the bacteria taxon. This enzyme is found predominantly in the organism ''Mycobacterium tuberculosis'', but also in ''Helicobacter pylori'', ''Bacteroides thetaiotaomicron'', ''Campylobacter jejuni'', ''Aquifex aeolicus'', ''Coxiella burnetii'', ''Arabidopsis thaliana''. This enzyme is a protein target for rational drug design against tuberculosis, which holds great potential due to shikimate kinase being absent in mammals. | ||
==Structure== | ==Structure== | ||
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===Ligands=== | ===Ligands=== | ||
ADP, CL, SKM | Ligands associated with shikimate kinase include ADP, CL, SKM, and TRS. | ||
Adenosine-5'-sisphosphate (ADP) | |||
Chloride ion (CL) | |||
(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-caroxylic acid (SKM) | |||
2-amino-2-hydroxymethyl-propane-1,3-diol (TRS) | |||
===Protein Fold=== | ===Protein Fold=== | ||
Protein folding from a random coil to native state with correct 3D structure is essential for proper protein function. The primary sequence of amino acids determines the folded structure. | |||
Shikimate kinase is a convenient protein to use in protein folding studies. This is because it is one of the smallest kinases and is a monomeric enzyme lacking disulfide bonds. It has been shown that the proposed refolding model includes a rapid hydrophobic collapse and then a slower secondary structure formation.<ref name="fold">The refolding of type II shikimate kinase from Erwinia chrysanthemi | |||
after denaturation in urea. European Journal of Biochemistry http://onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2002.ejb.02862.x/pdf</ref> | |||
Look into how the protein fold could be disrupted (ie pH, temperature studies etc) | |||
===Methods Used to Solve=== | ===Methods Used to Solve=== | ||
==Mechanism of Action== | ==Mechanism of Action== | ||
[[Image:Shikimate_kinase_reaction.png|400px|left|thumb| Shikimate kinase catalyzed reaction]] | |||
Describe how protein functions. Structures of Ligands/inhibitors/important steps in reaction pathway. | Describe how protein functions. Structures of Ligands/inhibitors/important steps in reaction pathway. | ||
The substrates involved with shikimate kinase are shikimate and ATP. The products involved are shikimate 3-phosphate and ADP. | |||
==Implications or Possible Application== | ==Implications or Possible Application== | ||
