Three sites and you are out: Ternary synergistic allostery controls aromatic amino acid biosynthesis in Mycobacterium tuberculosis.

3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids Trp, Phe, and Tyr. Unlike many other organisms that produce up to three isozymes, each feedback-regulated by one of the aromatic amino acid pathway end products, Mycobacterium tuberculosis expresses a single DAH7PS enzyme that can be controlled by combinations of aromatic amino acids. This study shows that the synergistic inhibition of this enzyme by a combination of Trp and Phe can be significantly augmented by the addition of Tyr.We used X-ray crystallography, mutagenesis, and isothermal titration calorimetry studies to show that DAH7PS from M. tuberculosis possesses a Tyr-selective site in addition to the Trp and Phe sites, revealing an unusual and highly sophisticated network of three synergistic allosteric sites on one enzyme. This ternary inhibitory response, by a combination of all three aromatic amino acids, allows a tunable response of the protein to changing metabolic demands

Structural mechanism of complex assemblies: Characterisation of beta-lactoglobulin and pectin interactions

Pectin and beta-lactoglobulin interact to form a hierarchical structure, which depends intimately on the tailored charge distribution on the pectin – and which causes the tertiary structure of the beta-lactoglobulin to change.</p

Anion-induced contraction of helical receptors

Uptake of a tetrafluoroborate anion into the centre of a dicopper bis-salicylaldoxime complex causes a major contraction of the cavity and an increase in helicity

A tetrameric structure is not essential for activity in dihydrodipicolinate synthase DHDPS from Mycobacterium tuberculosis.

Dihydrodipicolinate synthase DHDPS is a validated antibiotic target for which a new approach to inhibitor design has been proposed disrupting native tetramer formation by targeting the dimer dimer interface. In this study, rational design afforded a variant of Mycobacterium tuberculosis, Mtb DHDPS A204R, with disrupted quaternary structure. X ray crystallography at a resolution of 2.1 revealed a dimeric protein with an identical fold and active site structure to the tetrameric wild type enzyme. Analytical ultracentrifugation confirmed the dimeric structure in solution, yet the dimeric mutant has similar activity to the wild type enzyme. Although the affinity for both substrates was somewhat decreased, the high catalytic competency of the enzyme was surprising in the light of previous results showing that dimeric variants of the Escherichia coli and Bacillus anthracis DHDPS enzymes have dramatically reduced activity compared to their wild type tetrameric counterparts. These results suggest that Mtb DHDPS A204R is similar to the natively dimeric enzyme from S