William Lipscomb

Regulation in Yeast Chorismate Mutase, a Simple Allosteric Enzyme


Abstract

In the biosynthetic pathway to phenylalanine and tyrosine (only in plants, yeast, fungi, archaebacteria) chorismate is isomerized to prephrenate by chorismate mutase.

Inhibitors are candidates for herbicides, fungicides or bacteriocides. In another pathway chorismate leads to tryptophan. In yeast the activity of this enzyme is allosterically inhibited by tyrosine and stimulated by tryptophan to achieve a balance between these two biosynthetic pathways.

The yeast enzyme is a dimer (2 X 256 amino acids) in which one monomer rotates with respect to the other monomer by 15° as the less active T state (bound to Tyr) transforms to more active R state (bound to Trp). When a substrate analogue is bound a super-R state is formed in which this rotation is 22° away from the T state. Conformational changes will be described along the helix H8 (140-171) which extends from the regulatory site (where Tyr or Trp bind) to the active site (where the substrate analogue binds).

Catalytic activity is compared for the four known chorismate mutases: yeast (Harvard), B. subtilis (Harvard), E. coli (Cornell) and the much less active IF7 antibody (Scripps). Some 94 residues of the non-allosteric E. coli enzyme superimpose on the yeast enzyme (rms of 1.09 A). Very likely the allosteric yeast enzyme (2 X 256) arose from a gene doubling of the E. coli enzyme (2 X 109). The ether oxygen which breaks away from a ring carbon in chorismate is adjacent to Gln 88 in E. coli, but to Glu 246 in yeast. Possibly there is transient a protonation step in the yeast enzyme, but not in the E. coli, B. subilis or 1F7 antibody chorismate mutases.


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