8-Hydroxypenillic Acid from 6-Aminopenicillanic Acid: A New Reaction Catalyzed by a Class C β-Lactamase

Autor:	R. F. Pratt, Edith S. Wun, Marek Dryjanski, Vasilios M. Marathias
Rok vydání:	1996
Předmět:	chemistry.chemical_classification Carbamate Chemistry Bicarbonate medicine.medical_treatment General Chemistry Carbon-13 NMR Biochemistry Medicinal chemistry Catalysis Hydrolysis chemistry.chemical_compound Colloid and Surface Chemistry Enzyme Nucleophile medicine Methanol
Zdroj:	Journal of the American Chemical Society. 118:8207-8212
ISSN:	1520-5126 0002-7863
DOI:	10.1021/ja961685z
Popis:	The hydrolysis of 6-aminopenicillanic acid (APA) at neutral pH, catalyzed by the class C β-lactamase of Enterobacter cloacae P99, was observed from 1H NMR spectra to yield an unexpected product, 8-hydroxypenillic acid, in bicarbonate-containing buffers. This product probably arises from turnover of the carbamate of APA by the enzyme. 1H and 13C NMR spectra of APA in bicarbonate solutions clearly demonstrate the presence of the carbamate. Turnover of APA at saturating concentrations by the enzyme is accelerated by bicarbonate and by methanol. These results suggest that deacylation of the enzyme is rate determining and that the presence of the carbamate affects this step. A mechanism involving rate-determining intramolecular nucleophilic attack by the carbamate on the acyl enzyme is proposed to rationalize these observations and lead to formation of 8-hydroxypenillate. This reaction can be seen as an example of substrate-assisted enzymic catalysis. Quantitative analysis of the data indicated a dissociation ...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::c423eb942965dbc207ac3e691563fee3 https://doi.org/10.1021/ja961685z Zobrazit plný text záznamu