Indole-3-glycerol phosphate synthase, one of three consecutive (�/a)8-barrel enzymes in tryptophan biosynthesis, catalyzes the ring closure of 1-(o-carboxyphenylamino)-1-deoxyribulose-5-phosphate (CdRP) to indole-3-glycerol phosphate. Lys53, in the �1a1 loop, is a conserved residue that helps bind CdRP and may also be involved in correctly orienting the substrate for catalysis. These studies show that in a Lys53Arg mutation leads to a change in the rate-limiting step to the first ring closure step. Further analysis of a previously identified, coevolving interaction between the �1a1 and �2a2 loops is consistent with internal protein motions in the catalytic mechanism that facilitate the correct substrate orientation. Movement of Lys53 in the �1a1 loop can help gate the distance between the C1 and C2' carbons of CdRP, and other conformational changes in the �2a2 loop may have a role in the re-protonation of the general acid.

Understanding the catalytic function of enzyme dynamics in the active site loops of indole-3-glycerol phosphate synthase

244th National Meeting (2012)

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