Disease relevance of ECs3997

• Cloning, expression, purification, and characterization of biosynthetic threonine deaminase from Escherichia coli [1].
• Together, these data indicate that in E. coli Hcy toxicity is caused by a perturbation of branched-chain amino acid biosynthesis that is caused, at least in part, by the inhibition of threonine deaminase [2].
• Crystallization and preliminary X-ray crystallographic analysis of biodegradative threonine deaminase (TdcB) from Salmonella typhimurium [3].

High impact information on ECs3997

• TdcB, unlike the biosynthetic threonine deaminase, is insensitive to l-isoleucine and is activated by AMP [4].
• Biodegradative threonine deaminase (TdcB) catalyzes the first reaction in the anaerobic breakdown of l-threonine to propionate [4].
• In agreement with this behavior, D-cysteine inhibited the activity of threonine deaminase, a key enzyme of the isoleucine, leucine, and valine pathway [5].
• Shifts in the sigmoidal kinetics of allosteric threonine deaminase promoted by isoleucine and valine binding control branched chain amino acid biosynthesis in Escherichia coli [6].
• Enzyme kinetic data and isotherms for active site ligand binding to the mutants can be analyzed in terms of a simple two-state model to yield values for allosteric parameters that are consistent with previous estimates based on an expanded two-state model for homotropic cooperativity for threonine deaminase [6].

Chemical compound and disease context of ECs3997

• Feedback inhibition of the regulatory enzyme threonine deaminase by isoleucine provides an important level of enzymic control over branched chain amino acid biosynthesis in Escherichia coli [1].
• Cooperative binding of the feedback modifiers isoleucine and valine to biosynthetic threonine deaminase from Escherichia coli [7].
• The sigmoidal kinetics of alpha-ketobutyrate production catalyzed by threonine deaminase are shifted in the presence of the feedback inhibitor isoleucine and the activator valine to control carbon flow through branched-chain amino acid biosynthesis in Escherichia coli [8].
• Cysteine and growth inhibition of Escherichia coli: threonine deaminase as the target enzyme [9].
• Threonine deaminase from a nonsense mutant of Escherichia coli requiring isoleucine or pyridoxine: evidence for half-of-the-sites reactivity [10].

Biological context of ECs3997

• The increase in sigmoidal kinetics for the mutants relative to wild-type threonine deaminase may be attributable to the elimination of L-threonine binding to the effector sites, which activates the wild-type enzyme [6].
• Amino acid substitutions in the C-terminal regulatory domain disrupt allosteric effector binding to biosynthetic threonine deaminase from Escherichia coli [6].
• Threonine deaminase from Escherichia coli. II. Maturation and physical properties of the enzyme from a mutant altered in its regulation of gene expression [11].
• The regulation of the ilv ADGE operon: evidence for positive control by threonine deaminase [12].
• The enzyme formed under anaerobic conditions and known as threonine deaminase (biodegradative) is less widespread than threonine dehydrogenase and may be involved in energy metabolism rather than in threonine degradation per se [13].

Associations of ECs3997 with chemical compounds

• To a first approximation, the data are consistent with isoleucine and valine regulating threonine deaminase by shifting the allosteric equilibrium between the different affinity forms [8].
• The catalytic activity of threonine deaminase is absolutely dependent on the presence of pyridoxal phosphate, and the tetrameric molecule is isolated containing 1 mol of cofactor/56,000-Da chain [1].
• Wild-type threonine deaminase demonstrates a sigmoidal dependence of initial velocity on threonine concentration in the absence of isoleucine, consistent with a substrate-promoted conversion of the enzyme from a low activity to a high activity conformation [1].
• Both 2-aminobutyrate and alanine bind cooperatively to four sites on threonine deaminase, with an average dissociation constant of 12.7 and 43.8 mM, respectively [8].
• Valine treatment of nonstarved or methionine-starved cells led to the expected increase in threonine deaminase and transaminase B activities [14].

Analytical, diagnostic and therapeutic context of ECs3997

• The molecule weight of the biodegradative threonine deaminase from Escherichia coli was determined to be approximately 147,000 by sedimentation equilibrium ultracentrifugation [15].
• The effect of ligands on the fluorescence and circular dichroism spectra of the essential pyridoxal phosphate cofactor indicates that isoleucine and valine bind to effector sites that are distinct from the active sites in threonine deaminase [7].
• Evidence for two distinct effector-binding sites in threonine deaminase by site-directed mutagenesis, kinetic, and binding experiments [16].
• The activation of threonine deaminase from strain IP7 is due to a second coenzyme binding site, as shown by (i) spectrophotometric titration of the enzyme with pyridoxal phosphate and by (ii) measurement the pyridoxal phosphate content of the enzyme after sodium borohydride reduction of the protein [10].
• Polymorphous crystallization and diffraction of threonine deaminase from Escherichia coli [17].

References