Sandbox Reserved 763
From Proteopedia
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==Structure== | ==Structure== | ||
| - | The crystal structure of [[2iyq]] from the Protein Data Bank <ref>Protein Data Bank http://www.rcsb.org/pdb/explore.do?structureId=2IYQ</ref> showing shikimate kinase from ''Mycobacterium tuberculosis'' complexed with ADP and shikimate is shown to the right as the <scene name='56/564039/Defaultscene/1'>default scene</scene>. In addition, the 2D model of [[2gij]], showing the space filling details of the asymmetric unit of MtSK, is shown to the left. | + | The crystal structure of [[2iyq]] from the Protein Data Bank <ref name="PDB">Protein Data Bank http://www.rcsb.org/pdb/explore.do?structureId=2IYQ</ref> showing shikimate kinase from ''Mycobacterium tuberculosis'' complexed with ADP and shikimate is shown to the right as the <scene name='56/564039/Defaultscene/1'>default scene</scene>. 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=== | ===3D Structures in Different Organisms=== | ||
''Mycobacterium tuberculosis'' | ''Mycobacterium tuberculosis'' | ||
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===Active Residues=== | ===Active Residues=== | ||
| - | There are active residues where binding occurs. <ref name=" | + | There are active residues where binding occurs. |
| + | <ref name="PDB" /> | ||
Revision as of 18:36, 2 December 2013
| 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 |
Shikimate Kinase
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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, 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.
Oligomeric State
Through experiments involving size exclusion liquid chromatography and gel filtration chromatography, the oligomeric state of homogeneous MtSK was found. The molecular mass was found to be 20.7 kDa and when compared to the suggested value of 18.5 kDa, it was found that MtSK is a monomer in solution.[2]
Active Residues
There are active residues where binding occurs. [1]
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
- ↑ 1.0 1.1 Protein Data Bank http://www.rcsb.org/pdb/explore.do?structureId=2IYQ
- ↑ The Mode of Action of Recombinant Mycobacterium tuberculosis Shikimate Kinase: Kinetics and Thermodynamics Analyses http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061918
