Lettre du représentant Nioche, envoyé en mission dans le département d'Indre-et-Loire relative aux difficultés dans la fabrication du salpêtre dans la commune de Chinon, lors de la séance du 4 fructidor an II (21 août 1794)

Nioche Pierre Claude. Lettre du représentant Nioche, envoyé en mission dans le département d'Indre-et-Loire relative aux difficultés dans la fabrication du salpêtre dans la commune de Chinon, lors de la séance du 4 fructidor an II (21 août 1794). In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XCV - Du 26 thermidor au 9 fructidor an II (13 au 26 août 1794) Paris : Librairie Administrative P. Dupont, 1987. p. 329

Rapport fait à la Convention nationale, par P. C. Nioche, l'un des représentans du peuple envoyés près l'armée des Alpes, sur les malheureux événemens arrivés à Lyon le 29 mai 1793, l'an deuxième de la République française ([Reprod.])

Collection : Les archives de la Révolution française ; 6.2.253

Annonces concernant la prestation de serment des fonctionnaires publics ecclésiastiques des districts de Loches et Grenoble, lors de la séance du 26 février 1791

Bouche Charles-François, Barnave Antoine, Nioche Pierre-Claude. Annonces concernant la prestation de serment des fonctionnaires publics ecclésiastiques des districts de Loches et Grenoble, lors de la séance du 26 février 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXIII - Du 6 février 1791 au 9 mars 1791. Paris : Librairie Administrative P. Dupont, 1886. p. 537

Structural basis for substrate selectivity and nucleophilic substitution mechanisms in human adenine phosphoribosyltransferase catalyzed reaction

International audienceThe reversible adenine phosphoribosyltransferase enzyme (APRT) is essential for purine homeostasis in prokaryotes and eukaryotes. In humans, APRT (hAPRT) is the only enzyme known to produce AMP in cells from dietary adenine. APRT can also process adenine analogs, which are involved in plant development or neuronal homeostasis. However, the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction remains poorly understood. Here we present the crystal structures of hAPRT complexed to three cellular nucleotide analogs (hypoxanthine, IMP, and GMP) that we compare with the phosphate-bound enzyme. We established that binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. Furthermore , a quantum mechanics/molecular mechanics (QM/ MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (S N 2) with a mix of S N 1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted S N 2-type mechanism would be involved in the reverse reaction. These results provide a framework for understanding the molecular mechanism and substrate discrimination in both directions by APRTs. This knowledge can play an instrumental role in the design of inhibitors, such as antiparasitic agents, or adenine-based substrates

Structural Insights into the Forward and Reverse Enzymatic Reactions in Human Adenine Phosphoribosyltransferase

International audienceHighlights d Human APRT catalyzes the transformation of adenine into AMP and vice versa d Complexes with substrates in both directions of the reaction highlight key residues d The catalytic flexible loop dynamic is revealed by an in crystallo activity d Tyr105 is essential for cell growth by facilitating the forward reaction In Brief APRT is a key enzyme in the purine salvage pathway in prokaryotes and eukaryotes. Huyet et al., by using in vitro, cellular, and in crystallo enzymatic analyses, reveal that a hydroxyl group in a conserved tyrosine controls the protein dynamics and the catalytic efficiencies of the forward and reverse reactions