Premium
Allosteric inhibitor specificity of Thermotoga maritima 3‐deoxy‐ d ‐ arabino ‐heptulosonate 7‐phosphate synthase
Author(s) -
Cross Penelope J.,
Parker Emily J.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.07.044
Subject(s) - thermotoga maritima , allosteric regulation , shikimate pathway , atp synthase , chemistry , biochemistry , stereochemistry , biosynthesis , aromatic amino acids , amino acid , enzyme , gene , escherichia coli
3‐Deoxy‐ d ‐ arabino ‐heptulosonate 7‐phosphate synthase (DAH7PS) catalyses the first step of the shikimate pathway for the biosynthesis of aromatic amino acids. Allosteric regulation of Thermotoga maritima DAH7PS is mediated by l ‐Tyr binding to a discrete ACT regulatory domain appended to a core catalytic (β/α) 8 barrel. Variants of T. maritima DAH7PS ( Tma DAH7PS) were created to probe the role of key residues in inhibitor selection. Substitution Ser31Gly severely reduced inhibition by l ‐Tyr. In contrast both l ‐Tyr and l ‐Phe inhibited the Tma His29Ala variant, while the variant where Ser31 and His29 were interchanged (His29Ser/Ser31His), was inhibited to a greater extent by l ‐Phe than l ‐Tyr. These studies highlight the role and importance of His29 and Ser31 for determining both inhibitory ligand selectivity and the potency of allosteric response by Tma DAH7PS.