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=Chorismate Mutase= | =Chorismate Mutase= | ||
==Introduction== | ==Introduction== | ||
The gene Rv1885c from ''Mycobacteria tuberculosis'' encodes for a non-functional chorismate mutase (*MtCM).<ref name="pizza" /> This non-functional mutase has a 33-amino-acid cleavable sequence.<ref name="pizza" /> Chorismate mutase is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosine, and phenylalanine.<ref name="pizza" /> This protein acts at the first branch point of the shikimate pathway, making it a regulating step in the conversion of prephenate from chorismate.<ref name="CMW2"> PMID:11481470 </ref> Since chorismate mutase catalyzes a claisen rearrangement it can be considered an isomerase since it catalyzes rearrangements of isomers. Chorismate mutase provides a 2x10<sup>6</sup> fold increase in the rate of reaction in comparision 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> | The gene Rv1885c from ''Mycobacteria tuberculosis'' encodes for a non-functional chorismate mutase (*MtCM).<ref name="pizza" /> This non-functional mutase has a 33-amino-acid cleavable sequence.<ref name="pizza" /> Chorismate mutase is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosine, and phenylalanine.<ref name="pizza" /> This protein acts at the first branch point of the shikimate pathway, making it a regulating step in the conversion of prephenate from chorismate.<ref name="CMW2"> PMID:11481470 </ref> Since chorismate mutase catalyzes a claisen rearrangement it can be considered an isomerase since it catalyzes rearrangements of isomers. Chorismate mutase provides a 2x10<sup>6</sup> fold increase in the rate of reaction in comparision 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> | ||
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" /> It is believed that a pseudoperiplasmic space might exist in ''M. tuberculosis''.<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" /> It is believed that a pseudoperiplasmic space might exist in ''M. tuberculosis''.<ref name="pizza" /> | ||
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in Michaelis-Menten kinetics chorismate mutase has Km of 0.5 ± 0.05 mM and Kcat of 60 s<sup>-1 </sup>.<ref name="pizza" /> | in Michaelis-Menten kinetics chorismate mutase has Km of 0.5 ± 0.05 mM and Kcat of 60 s<sup>-1 </sup>.<ref name="pizza" /> | ||
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 rearrangement.<ref name="pizza" / > First by converting chorismate to prephenate.<ref name="pizza" /> Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate.<ref name="pizza" / > After this occurs, aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine.<ref name="pizza" /> 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 rearrangement.<ref name="pizza" /> First by converting chorismate to prephenate.<ref name="pizza" /> Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate.<ref name="pizza" /> After this occurs, aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine.<ref name="pizza" /> 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 has optimal performance at 37 degrees Celcius and at pH 7.5, but it can still optimally a pH range from pH 4.0 to 7.5 <ref name="pizza" /> | Chorismate mutase has optimal performance at 37 degrees Celcius and at pH 7.5, but it can still optimally a pH range from pH 4.0 to 7.5 <ref name="pizza" /> | ||
==Chorismate Mutase and Tuberculosis== | ==Chorismate Mutase and Tuberculosis== | ||
Tuberculosis has developed various mechanisms to survive in hostile environments.<ref name="CMArt2" /> The emergence of multi-drug resistant tuberculosis and other diseases such as AIDS compound the problem of how to treat tuberculosis.<ref name="CMArt2" /> Chorismate mutase may be involved in pathogenesis.<ref name="pizza" /> Researchers are currently looking into new antimicrobial drugs for diseases such as tuberculosis.<ref name="pizza" /> These new drugs would take advantage of the fact that chorismate mutase and the shikimate pathway do not occur in humans, to target and treat various forms of tuberculosis.<ref name="pizza" /> Chorismate mustase is believed to have a role in the survival of ''M. tuberculosis''.<ref name="CMArt2" /> Two genes in ''M. tuberculosis'', Rv0948c and Rv1885c code for chorismate mutase.<ref name="CMArt2" /> These help support ''M. tuberculosis'' when aromatic amino acids, such as tryptophan, tyrosine, and phenylalanine, are deficient.<ref name="CMArt2" /> Some researchers have proposed that a proline-rich section of ''M. tuberculosis'' chorismate mutase might be responsible for it binding to the surface receptors on the host cell marcophages | Tuberculosis has developed various mechanisms to survive in hostile environments.<ref name="CMArt2" /> The emergence of multi-drug resistant tuberculosis and other diseases such as AIDS compound the problem of how to treat tuberculosis.<ref name="CMArt2" /> Chorismate mutase may be involved in pathogenesis.<ref name="pizza" /> Researchers are currently looking into new antimicrobial drugs for diseases such as tuberculosis.<ref name="pizza" /> These new drugs would take advantage of the fact that chorismate mutase and the shikimate pathway do not occur in humans, to target and treat various forms of tuberculosis.<ref name="pizza" /> Chorismate mustase is believed to have a role in the survival of ''M. tuberculosis''.<ref name="CMArt2" /> Two genes in ''M. tuberculosis'', Rv0948c and Rv1885c code for chorismate mutase.<ref name="CMArt2" /> These help support ''M. tuberculosis'' when aromatic amino acids, such as tryptophan, tyrosine, and phenylalanine, are deficient.<ref name="CMArt2" /> Some researchers have proposed that a proline-rich section of ''M. tuberculosis'' chorismate mutase might be responsible for it binding to the surface receptors on the host cell marcophages | ||
.<ref name="CMW1"> PMID: 16752890 </ref> | .<ref name="CMW1"> PMID: 16752890 </ref> | ||
==References== | ==References== | ||
<references/> | <references/> | ||
