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This Sandbox is Reserved from Sep 25, 2013, through Mar 31, 2014 for use in the course "BCH455/555 Proteins and Molecular Mechanisms" taught by Michael B. Goshe at the North Carolina State University. This reservation includes Sandbox Reserved 299, Sandbox Reserved 300 and Sandbox Reserved 760 through Sandbox Reserved 779.

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Contents 1 Shikimate Kinase 1.1 Structure 1.1.1 3D Structures in Different Organisms 1.1.2 Secondary Structural Elements 1.1.3 Oligomeric State 1.1.4 Active Residues 1.1.5 Ligands 1.1.6 Protein Fold 1.1.7 Methods Used to Solve 1.2 Mechanism of Action 1.3 Implications or Possible Application 1.4 References

Shikimate Kinase

spinqualitylabelsall models Crystal structure of 2iyq from Protein Data Bank showing shikimate kinase from Mycobacterium tuberculosis complexed with ADP and shikimate. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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, 5 strands, and is typically 176 amino acids in length. The subunit is that of a monomer and it is found in the cytoplasm. 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

The crystal structure of 2iyq from the Protein Data Bank ^[1] showing shikimate kinase from Mycobacterium tuberculosis complexed with ADP and shikimate is shown to the right as the . In addition, the 2D model of 2gij, showing the space filling details of the asymmetric unit of MtSK, is shown to the left.

3D Structures in Different Organisms

Mycobacterium tuberculosis

2g1j - MtSK

2iyt - MtSK (unliganded, open lid)

1iyw - MtSK (open lid) + ATP

2g1k, 2iyr, 2iyx - MtSK + shikimate

2iys - MtSK (open lid) + shikimate

2iyy - MtSK + shikimate-3-phosphate

2iys - MtSK (open lid) + shikimate

2iyu, 2iyv - MtSK (open lid) + ADP

1l4u, 1l4y, 1u8a, 2dft - MtSK + ADP

2iyw - MtSK (open lid) + ATP

3baf - MtSK + AMP-PNP

2dfn, 1we2, 2iyq, 1u8a - MtSK + ADP + shikimate

2iyz - MtSK + ADP + shikimate-3-phosphate

4bqs - MtSK + ADP + shikimic acid derivative

1zyu - MtSK + AMPPCP + shikimate

Helicobacter pylori

1zuh - HpSK

3mrs - HpSK (mutant)

1zui - HpSK + shikimate

3n2e - HpSK (mutant) + inhibitor

3muf - HpSK + ADP + shikimate-3-phosphate

Other Organisms

2pt5 - SK - Aquifex Aeolicus

3trf - SK - Coxiella burnetii

3vaa - SK - Bacteroides thetaiotaomicron

1via - SK - Campylobacter jejuni

3nwj - SK - Arabidopsis thaliana

Secondary Structural Elements

Using 2iyq as an example, the secondary structure of shikimate kinase can be observed in terms of strands and helices shown. There are 5 strands, shown in yellow, and 9 helices, shown in pink. strands shown in yellow and helices in pink.

Oligomeric State

Active Residues

Ligands

ADP, CL, SKM

Protein Fold

Methods Used to Solve

Mechanism of Action

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

Implications or Possible Application

Medical importance - related disease, if used as drug target.

If protein is found in other organisms.

Other uses (ie antibiotics etc)

References