Sandbox Reserved 325
From Proteopedia
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==Introduction== | ==Introduction== | ||
The gene Rv1885c from ''Mycobacteriam tuberculosis'' encodes for a non-functional chorismate mutase (*MtCM)<ref name="pizza" />. This non-functional mutase has a 33-amino-acid cleavable sequence. It is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosinem and phenylalanine <ref name="pizza" />. Chorismate mutase only occurs in bacteria, higher plants, and fungi, due to the fact that the shikimate pathway is only found in these organisms <ref name="strat" />. In ''Escherichia coli'', chorismate mutase has a periplasmic destination<ref name="pizza" />. In ''M. tuberculosis'' there is in abscence of a periplasmic compartment for chorismate mutase, so it secretes into the culture filtrate of ''M. tuberculosis''<ref name="pizza" /> | The gene Rv1885c from ''Mycobacteriam tuberculosis'' encodes for a non-functional chorismate mutase (*MtCM)<ref name="pizza" />. This non-functional mutase has a 33-amino-acid cleavable sequence. It is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosinem and phenylalanine <ref name="pizza" />. Chorismate mutase only occurs in bacteria, higher plants, and fungi, due to the fact that the shikimate pathway is only found in these organisms <ref name="strat" />. In ''Escherichia coli'', chorismate mutase has a periplasmic destination<ref name="pizza" />. In ''M. tuberculosis'' there is in abscence of a periplasmic compartment for chorismate mutase, so it secretes into the culture filtrate of ''M. tuberculosis''<ref name="pizza" /> | ||
| + | Rv1185c is synthesized along with an amino acid terminal sequence, which is cleaved off from the mature protein when expressed with e coli | ||
Chorismate mutase is an essential enzyme in the shikimate pathway <ref name="pizza"> PMID:17146044 </ref>. This pathway allows for the biosynthesis of aromatic amino acids tryptophan, tyrosine, and phenylalanine <ref name="pizza" />. The production of tyrosine and phenylalanine is achieved by what is called a Claisen arrangement. first converting chorismate to prephenate. Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate. After this occursm aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine. Chorismate mutase provides a 2x10<sup>6</sup> fold increase in the rate of reaction, in comparison to the uncatalyzed reaction <ref > P.D. Lyne, A.J. Mulholland, W.G. Richards. Insights into chorismate mutase catalysis from a combined qm/mm simulation of the enzyme reaction. Journal of the American Chemistry Society. 1995 117(45):11345-11350</ref>. It is the only example of an enzyme catalyzing a percyclic reaction <ref name="strat"> PMID:10960481 </ref> | Chorismate mutase is an essential enzyme in the shikimate pathway <ref name="pizza"> PMID:17146044 </ref>. This pathway allows for the biosynthesis of aromatic amino acids tryptophan, tyrosine, and phenylalanine <ref name="pizza" />. The production of tyrosine and phenylalanine is achieved by what is called a Claisen arrangement. first converting chorismate to prephenate. Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate. After this occursm aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine. Chorismate mutase provides a 2x10<sup>6</sup> fold increase in the rate of reaction, in comparison to the uncatalyzed reaction <ref > P.D. Lyne, A.J. Mulholland, W.G. Richards. Insights into chorismate mutase catalysis from a combined qm/mm simulation of the enzyme reaction. Journal of the American Chemistry Society. 1995 117(45):11345-11350</ref>. It is the only example of an enzyme catalyzing a percyclic reaction <ref name="strat"> PMID:10960481 </ref> | ||
==Structure== | ==Structure== | ||
| - | has dimeric state in concentrations as low as 5nM | ||
| - | has an all alpha helical structure | ||
| - | active site forms in single chain without help from second half of dimer | ||
| - | |||
<Structure load='2f6l' size='300' frame='true' align='left' caption='Insert caption here' scene='Sandbox_Reserved_325/Chainbows/1' /> | <Structure load='2f6l' size='300' frame='true' align='left' caption='Insert caption here' scene='Sandbox_Reserved_325/Chainbows/1' /> | ||
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has an all alpha helical structure | has an all alpha helical structure | ||
active site forms in single chain without help from second half of dimer | active site forms in single chain without help from second half of dimer | ||
| + | active site is critical for catalysis. it is made up of Arg 49, Lys 60, Arg 72, Thr 105, Glu 109, and Arg 134 | ||
| + | not regulated by aromatic amino acids, which is supported by the fact that there are no allosteric regulatory sites. | ||
| + | alpha helicalstruc similar to e coli CM and S. cerevisae CM | ||
here is a <scene name='Sandbox_Reserved_325/Disulfide/1'>disulfide bridge</scene> | here is a <scene name='Sandbox_Reserved_325/Disulfide/1'>disulfide bridge</scene> | ||
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==Chorismate Mutase and Tuberculosis== | ==Chorismate Mutase and Tuberculosis== | ||
| - | + | may be involved in pathogenesis. | |
| + | one can take advantage of non-occurance of CMs in humans to try to develop antimicrobial drugs for human pathogens such as tb | ||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 04:48, 2 April 2011
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| 2f6l, resolution 1.70Å () | |||||||||
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| Gene: | Rv1885c (Mycobacterium tuberculosis) | ||||||||
| Activity: | Chorismate mutase, with EC number 5.4.99.5 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
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Contents |
Chorismate Mutase
Introduction
The gene Rv1885c from Mycobacteriam tuberculosis encodes for a non-functional chorismate mutase (*MtCM)[1]. This non-functional mutase has a 33-amino-acid cleavable sequence. It is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosinem and phenylalanine [1]. Chorismate mutase only occurs in bacteria, higher plants, and fungi, due to the fact that the shikimate pathway is only found in these organisms [2]. In Escherichia coli, chorismate mutase has a periplasmic destination[1]. In M. tuberculosis there is in abscence of a periplasmic compartment for chorismate mutase, so it secretes into the culture filtrate of M. tuberculosis[1] Rv1185c is synthesized along with an amino acid terminal sequence, which is cleaved off from the mature protein when expressed with e coli
Chorismate mutase is an essential enzyme in the shikimate pathway [1]. This pathway allows for the biosynthesis of aromatic amino acids tryptophan, tyrosine, and phenylalanine [1]. The production of tyrosine and phenylalanine is achieved by what is called a Claisen arrangement. first converting chorismate to prephenate. Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate. After this occursm aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine. Chorismate mutase provides a 2x106 fold increase in the rate of reaction, in comparison to the uncatalyzed reaction [3]. It is the only example of an enzyme catalyzing a percyclic reaction [2]
Structure
|
has dimeric state in concentrations as low as 5nM has an all alpha helical structure active site forms in single chain without help from second half of dimer active site is critical for catalysis. it is made up of Arg 49, Lys 60, Arg 72, Thr 105, Glu 109, and Arg 134 not regulated by aromatic amino acids, which is supported by the fact that there are no allosteric regulatory sites.
alpha helicalstruc similar to e coli CM and S. cerevisae CM
here is a
Mechanism
in michaelis menten kinetics it has Km of 0.5 ± 0.05 mM and Kcat of 60 s-1 Chorismate mutase is an essential enzyme in the shikimate pathway [1]. This pathway allows for the biosynthesis of aromatic amino acids tryptophan, tyrosine, and phenylalanine [1]. The production of tyrosine and phenylalanine is achieved by what is called a Claisen arrangement. first converting chorismate to prephenate. Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate. After this occursm aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine. Chorismate mutase provides a 2x106 fold increase in the rate of reaction, in comparison to the uncatalyzed reaction [4]. It is the only example of an enzyme catalyzing a percyclic reaction [2]
Chorismate Mutase and Tuberculosis
may be involved in pathogenesis. one can take advantage of non-occurance of CMs in humans to try to develop antimicrobial drugs for human pathogens such as tb
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Kim SK, Reddy SK, Nelson BC, Vasquez GB, Davis A, Howard AJ, Patterson S, Gilliland GL, Ladner JE, Reddy PT. Biochemical and structural characterization of the secreted chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv: an *AroQ enzyme not regulated by the aromatic amino acids. J Bacteriol. 2006 Dec;188(24):8638-48. PMID:17146044 doi:188/24/8638
- ↑ 2.0 2.1 2.2 Kast P, Grisostomi C, Chen IA, Li S, Krengel U, Xue Y, Hilvert D. A strategically positioned cation is crucial for efficient catalysis by chorismate mutase. J Biol Chem. 2000 Nov 24;275(47):36832-8. PMID:10960481 doi:10.1074/jbc.M006351200
- ↑ P.D. Lyne, A.J. Mulholland, W.G. Richards. Insights into chorismate mutase catalysis from a combined qm/mm simulation of the enzyme reaction. Journal of the American Chemistry Society. 1995 117(45):11345-11350
- ↑ P.D. Lyne, A.J. Mulholland, W.G. Richards. Insights into chorismate mutase catalysis from a combined qm/mm simulation of the enzyme reaction. Journal of the American Chemistry Society. 1995 117(45):11345-11350
