Sandbox Reserved 325: Difference between revisions

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 <ref name="pizza" />. It is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosinem 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:PMC55368 </ref>.  Chorismate mutase provides a 2x10⁶ fold increase in the rate of reacrion 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" />. The N-terminal sequence of ''M. tuberculosis'' chorismate mutase is able to  function in ''E. coli'' which suggests that ''M. tuberulosis'' chorismate mutase belongs to the AroQ class of the chorismate mutases<ref name="CMArt2"> PMID:15737998 </ref>. Rv1885c is synthesized along with the 33-amino-acid terminal sequence, which when expressed with ''E. coli'', is cleaved off the mature protein<ref name="pizza"  />.  Chorismate mutase is the only example of an enzyme catalyzing a percyclic reaction <ref name="strat"> PMID:10960481 </ref>

Chorismate mutase is a homodimer which has an all-α-helical structure <ref name="pizza" />.  There are 10 α-helicies spread across the two monomers of chorismate mutase <ref name="pizza" />.  The α-helical structure of ''M. tuberculosis'' chorismate mustase similar to the chorismate mutases of ''S. cerevisae'' and ''E. coli''.  It holds its dimeric state in a protein concentration as low as 5 nM <ref name="pizza" />. Chorismate has an active site, which is used for the catalysis of the shikimate pathway <ref name="pizza" />.  The active site is made of Arg ₄₉,Lys ₆₀, Arg ₇₂, Thr ₁₀₅, Glu ₁₀₉, and Arg ₁₃₄<ref name="pizza" />. This active site exists through electrostatic interactions with chorismate and hydrogen bonding between the amino acids <ref name="CMW2" />.  The active site forms within a single chain <ref name="pizza" />.  The active site can form without any help from the second half of the dimer <ref name="pizza" />.  The molecular weight of chorismate mutase is 36,000 Da <ref name="pizza" />.  Based on the fact that each monomeric subunit has a molecular weight of 18,474 Da, the molecular weight of the molecule supports the theory that it is a dimer <ref name="pizza" />.