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Isopentenyl Diphosphate Inhibition of Thiamin Diphosphate Enzymes, Especially Deoxyxylulose 5‐Phosphate Synthase
Author(s) -
Sharkey Thomas,
Banerjee Aparajita,
Cheaney Laura
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.887.20
Subject(s) - enzyme , transketolase , thiamine , chemistry , biochemistry , atp synthase , alanine , stereochemistry , amino acid
Isopentenyl diphosphate (IDP) and dimethylallyl diphosphate compete with thiamin diphosphate (ThDP) thereby reducing the activity of deoxyxylulose 5‐phosphate synthase (DXS). Studies of this phenomenon were extended to test modifications of DXS that might show reduced inhibition, removing a feedback that limits the usefulness of the methyl erythritol 4‐phosphate (MEP) pathway in biotechnological efforts. A predicted enzyme structure was examined to find ligand‐enzyme interactions relatively more important for IDP‐enzyme interactions than ThDP‐enzyme interactions. Two alanine residues important for binding ThDP and IDP were mutated to glycine. In one case the IDP inhibition was reduced and overall activity increased. This provides proof of concept that it is possible to reduce the feedback from IDP on DXS activity. We also tested other ThDP‐dependent enzymes for inhibition by IDP. Pyruvate decarboxylase and transketolase also showed inhibition by IDP. This research was supported by National Science Foundation Grant IOS‐0950574.