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Inhibition studies of porphobilinogen synthase from Escherichia coli differentiating between the two recognition sites
Auteur(s)
Stauffer, Frédéric
Zizzari, Eleonor
Jarret, Caroline
Faurite, Jean-Philippe
Bobalova, Janette
Date de parution
2001
In
Chembiochem
Vol.
5
No
2
De la page
343
A la page
354
Résumé
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.
Identifiants
Type de publication
Resource Types::text::journal::journal article
