Vignette d'image

Neier, Reinhard

Nom
Neier, Reinhard
Affiliation principale
Fonction
Professeure ordinaire
Email
Reinhard.Neier@unine.ch
Identifiants
https://libra.unine.ch/handle/123456789/383
_
0000-0003-0890-1797

Résultat de la recherche

Filtres

11
4
31
31
Réinitialiser les filtres

Paramètres

Voici les éléments 1 - 4 sur 4
  • Publication
    Métadonnées seulement
    Inhibition studies of porphobilinogen synthase from Escherichia coli differentiating between the two recognition sites
    (2001)
    Stauffer, Frédéric
    ;
    Zizzari, Eleonor
    ;
    Jarret, Caroline
    ;
    Faurite, Jean-Philippe
    ;
    Bobalova, Janette
    ;
    Neier, Reinhard 
    Porphobilinogen synthase condenses two molecules of 5-amino-levulinate in an asymmetric way. This unusual transformation requires a selective recognition and differentiation between the :substrates ending up in the A site or in the P site of porphobilinogen synthase. Studies of inhibitors based on the key intermediate first postulated by Jordan allowed differentiation of the two recognition sites. The P site, whose structure is known from X-ray crystallographic studies, tolerates ester functions well. The A site interacts very strongly with nitro groups, but is not very tolerant to ester functions. This differentiation is a central factor in the asymmetric I handling of the two identical substrates. Finally, it could be shown nor the keto group of-the,Substrate bound at the A site is not Only essential for the recognition, but that an increase in electrophilicity of-the carbon atom also increases the inhibition potency considerably. This has important consequences for the recognition process at the A site, whose-exact structure is not yet known.
  • Publication
    Accès libre
    Inhibition of Escherichia coli porphobilinogen synthase using analogs of postulated intermediates
    (2000)
    Jarret, Caroline
    ;
    Stauffer, Frédéric
    ;
    Henz, Matthias E
    ;
    Marty, Maurus
    ;
    Lüönd, Rainer M
    ;
    Bobálová, Janette
    ;
    Schürmann, Peter
    ;
    Neier, Reinhard 
    Background: Porphobilinogen synthase is the second enzyme involved in the biosynthesis of natural tetrapyrrolic compounds, and condenses two molecules of 5-aminolevulinic acid (ALA) through a nonsymmetrical pathway to form porphobilinogen. Each substrate is recognized individually at two different active site positions to be regioselectively introduced into the product. According to pulse-labeling experiments, the substrate forming the propionic acid sidechain of porphobilinogen is recognized first. Two different mechanisms for the first bond-forming step between the two substrates have been proposed. The first involves carbon–carbon bond formation (an aldol-type reaction) and the second carbon–nitrogen bond formation, leading to an iminium ion.
    Results: With the help of kinetic studies, we determined the Michaelis constants for each substrate recognition site. These results explain the Michaelis–Menten behavior of substrate analog inhibitors — they act as competitive inhibitors. Under standard conditions, however, another set of inhibitors demonstrates uncompetitive, mixed, pure irreversible, slow-binding or even quasi-irreversible inhibition behavior.
    Conclusions: Analysis of the different classes of inhibition behavior allowed us to make a correlation between the type of inhibition and a specific site of interaction. Analyzing the inhibition behavior of analogs of postulated intermediates strongly suggests that carbon–nitrogen bond formation occurs first.
  • Publication
    Métadonnées seulement
    Inhibition Studies of Porphobilinogen Synthase from Escherichia coli Using Diacids
    (: Imperial College Press, 1998)
    Jarret, Caroline
    ;
    Bobalova, Janette
    ;
    Stauffer, Frédéric
    ;
    Henz, Matthias
    ;
    Neier, Reinhard 
    ;
    Rzepa, H.J.
    ;
    Kappe, O.
  • Publication
    Métadonnées seulement
    Inhibition of porphobilinogen synthase (PBG-synthase) by 4,6-dioxoheptanoic acid and related compounds
    (1998)
    Stauffer, Frederic
    ;
    Jarret, Caroline
    ;
    Engeloch, Thomas
    ;
    Henz, Matthias
    ;
    Bobalova, Janette
    ;
    Neier, Reinhard 
    We are investigating the mechanism of PBG-synthase by active site directed inhibition studies. The procedure for testing and the data obtained with compds. related to 4,6-dioxoheptanoic acid are reported and the results are discussed in the context of our kinetic model. [on SciFinder(R)]