Some chemical properties and biological role of thiazolidine compounds

Terzuoli, Lucia; Leoncini, Roberto; Pagani, Roberto; Guerranti, Roberto; Vannoni, Davide; Ponticelli, Fabio; Marinello, Enrico

doi:10.1016/s0024-3205(98)00387-7

Cited by 17 publications

(24 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, after dialysis of the enzyme thiazolidine complex, the 335 nm peak decreased and the 421 nm peak was regenerated, indicating that thiazolidine formation is reversible ( Figure 4 B, inset). Reversibility of thiazolidine formation has been reported previously [ 18 , 20 , 21 , 23 , 24 , 25 ].…”

Section: Resultsmentioning

confidence: 75%

Functional Characterization and Structure-Guided Mutational Analysis of the Transsulfuration Enzyme Cystathionine γ-Lyase from Toxoplasma gondii

Maresi

Janson

Fruncillo

et al. 2018

IJMS

View full text Add to dashboard Cite

Sulfur-containing amino acids play essential roles in many organisms. The protozoan parasite Toxoplasma gondii includes the genes for cystathionine β-synthase and cystathionine γ-lyase (TgCGL), as well as for cysteine synthase, which are crucial enzymes of the transsulfuration and de novo pathways for cysteine biosynthesis, respectively. These enzymes are specifically expressed in the oocyst stage of T. gondii. However, their functionality has not been investigated. Herein, we expressed and characterized the putative CGL from T. gondii. Recombinant TgCGL almost exclusively catalyses the α,γ-hydrolysis of l-cystathionine to form l-cysteine and displays marginal reactivity toward l-cysteine. Structure-guided homology modelling revealed two striking amino acid differences between the human and parasite CGL active-sites (Glu59 and Ser340 in human to Ser77 and Asn360 in toxoplasma). Mutation of Asn360 to Ser demonstrated the importance of this residue in modulating the specificity for the catalysis of α,β- versus α,γ-elimination of l-cystathionine. Replacement of Ser77 by Glu completely abolished activity towards l-cystathionine. Our results suggest that CGL is an important functional enzyme in T. gondii, likely implying that the reverse transsulfuration pathway is operative in the parasite; we also probed the roles of active-site architecture and substrate binding conformations as determinants of reaction specificity in transsulfuration enzymes.

show abstract

Section: Resultsmentioning

confidence: 75%

Functional Characterization and Structure-Guided Mutational Analysis of the Transsulfuration Enzyme Cystathionine γ-Lyase from Toxoplasma gondii

Maresi

Janson

Fruncillo

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Reactions of PLP with amino groups of proteins can alter their structure and at concentrations of 10 to 100 μM inhibit enzyme activity and aldehydes can damage DNA leading to mutagenesis . PLP can also react with small molecules including sulphydryl compounds such as cysteine resulting in the formation of thiazoliodines and with sulfite producing a sulphonate. The aldehyde group of PLP can also react, via Knoevenagel condensation, with Δ 1 ‐pyrroline 5‐carboxylate and Δ 1 ‐piperideine 6‐carboxylate.…”

Section: Reactivitymentioning

confidence: 99%

Disorders affecting vitamin B₆ metabolism

Wilson¹,

Plecko²,

Mills³

et al. 2019

J of Inher Metab Disea

169

186

View full text Add to dashboard Cite

Vitamin B6 is present in our diet in many forms, however, only pyridoxal 5′‐phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs nonphosphorylated B6 vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Pathways reliant on PLP include amino acid and neurotransmitter metabolism, folate and 1‐carbon metabolism, protein and polyamine synthesis, carbohydrate and lipid metabolism, mitochondrial function and erythropoiesis. Besides the role of PLP as a cofactor B6 vitamers also play other cellular roles, for example, as antioxidants, modifying expression and action of steroid hormone receptors, affecting immune function, as chaperones and as an antagonist of Adenosine‐5'‐triphosphate (ATP) at P2 purinoceptors. Because of the vital role of PLP in neurotransmitter metabolism, particularly synthesis of the inhibitory transmitter γ‐aminobutyric acid, it is not surprising that various inborn errors leading to PLP deficiency manifest as B6‐responsive epilepsy, usually of early onset. This includes pyridox(am)ine phosphate oxidase deficiency (a disorder affecting PLP synthesis and recycling), disorders affecting PLP import into the brain (hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects), a disorder of an intracellular PLP‐binding protein (PLPBP, previously named PROSC) and disorders where metabolites accumulate that inactivate PLP, for example, ALDH7A1 deficiency and hyperprolinaemia type II. Patients with these disorders can show rapid control of seizures in response to either pyridoxine and/or PLP with a lifelong dependency on supraphysiological vitamin B6 supply. The clinical and biochemical features of disorders leading to B6‐responsive seizures and the treatment of these disorders are described in this review.

show abstract

“… 22 , 146 , 147 This amino acid functions by mimicking the natural l -serine substrate; when in the active site, cysteine forms a PLP:amino acid external aldimine complex, but then readily reacts to form a ring-closed, thiazolidine–PLP compound. 21 , 148 , 149 This results in irreversible modification of the PLP cofactor, rendering the enzyme non-catalytic. The inhibitor l -penicillamine behaves in a similar manner to cysteine by forming a thiazolidine adduct with the PLP cofactor, inhibiting the enzyme.…”

Section: Serine Palmitoyltransferase (Spt)mentioning

confidence: 99%