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Corine Mas-Droux

Threonine synthase and Aspartate kinase. Structural study of two allosteric enzymes controlled by S-adenosylmethionine

Published on 4 January 2006


Thesis presented January 04, 2006

Abstract:
Threonine synthase (TS) and Aspartate kinase (AK) are two allosteric enzymes involved in the amino acid derived from aspartate pathway. Two isoforms of TS and three isoforms of AK exist in Arabidopsis thaliana. Kinetics studies shown that S-adenosylmethionine (SAM) is a plant specific allosteric effector of the two isoforms of TS and one isoform of AK (AK 1). TS activity are stimulated by SAM whereas for AK 1 SAM reinforces the inhibition by lysine. In the aim to describe, at a molecular level, the allosteric regulation of these two enzymes and to understand how the SAM specificity appears in plant, we undertake a structural study of these two proteins.
The crystallographic structure of Arabidopsis thaliana TS complexed with its cofactor, pyridoxal phosphate (PLP) shows that a non classical position of PLP, for a fold II type PLP dependent enzyme, explains the low activity and low affinity of TS for its substrate without SAM. The Arabidopsis thaliana TS structure achieved with SAM and PLP reveals asymmetric conformational changes leading to the site activation of only monomer in the dimer.
The crystallographic structure of AK 1 displays, for the first time, the structural organization of an Aspartate kinase. This enzyme, which holds two ACT domains, shows a new kind or organization for an ACT regulatory domain. This structure was obtained with the two allosteric inhibitors (lysine and SAM) reveals the inactive form of the enzyme.

Keywords:
Threonine synthase​, Aspartate kinase, Arabidopsis thaliana, ACT regulatory domain, S-Adenosylmethionine, allostery