Feedback inhibition of enzyme activity:

• Two enzymes are used for the isomerization of chorismate in the shikimate pathway: one that also dehydrogenates to hydroxyphenylpyruvate and one that instead dehydrates to phenylpyruvate.
  

• These enzymes are feedback inhibited by the amino acid to which their product is converted.

• The dehydrogenase leading to hydroxyphenylpyruvate is inhibited by a tyrosine bound in an allosteric site.

  T-State of Chorismate Mutase (Yeast)
  The tyrosine is at lower left; the active site is in orange at upper right

• The classic example of an allosteric regulatory enzyme is aspartate transcarbamoylase, which catalyzes the first committed step in the biosynthesis of pyrimidine nucleotides.
  • ATC is subject to both allosteric inhibition and allosteric activation.

  • It is inhibited by cytidine triphosphate, the end product of its biosynthetic pathway. The structure on the left, below shows the T-state with a bound CTP.

  • ATP, the end product of the purine biosynthetic pathway, activates the enzyme, probably to make sure that purine and pyrimidine synthesis stay in balance.

  Aspartate Transcarbamoylase, T-state (Cytidine triphosphate bound)	Aspartate Transcarbamoylase, R-state (Phosphonacetyl aspartate bound)

• The two CTPs are bound at the top, near where the two lobes of the enzyme join. The substrate analogs are bound at the bottom, in each lobe.

• The term "allosteric" implies that a conformational change is involved. Here is a superposition of the T- (pink) and the R- (blue) states:
  

• Even though the sequence is identical, these superpose with an rmsd of 2.02 A.