103 research outputs found
Phosphonodifluoropyruvate is a mechanism-based inhibitor of phosphonopyruvate decarboxylase from Bacteroides fragilis
Bacteroides fragilis, a human pathogen, helps in the formation of intra-abdominal abscesses and is involved in 90% of anaerobic peritoneal infections. Phosphonopyruvate decarboxylase (PnPDC), a thiamin diphosphate (ThDP)-dependent enzyme, plays a key role in the formation of 2-aminoethylphosphonate, a component of the cell wall of B. fragilis. As such PnPDC is a possible target for therapeutic intervention in this, and other phosphonate producing organisms. However, the enzyme is of more general interest as it appears to be an evolutionary forerunner to the decarboxylase family of ThDP-dependent enzymes. To date, PnPDC has proved difficult to crystallize and no X-ray structures are available. In the past we have shown that ThDP-dependent enzymes will often crystallize if the cofactor has been irreversibly inactivated. To explore this possibility, and the utility of inhibitors of phosphonate biosynthesis as potential antibiotics, we synthesized phosphonodifluoropyruvate (PnDFP) as a prospective mechanism-based inhibitor of PnPDC. Here we provide evidence that PnDFP indeed inactivates the enzyme, that the inactivation is irreversible, and is accompanied by release of fluoride ion, i.e., PnDFP bears all the hallmarks of a mechanism-based inhibitor. Unfortunately, the enzyme remains refractive to crystallization
Preparation of Nucleosides Derived from 2-Nitroimidazole and d-Arabinose, d-Ribose, and d-Galactose by the VorbrĂĽggen Method and Their Conversion to Potential Precursors for Tracers To Image Hypoxia
Fungitoxicidade, atividade elicitora de fitoalexinas e proteção de pepino contra Colletotrichum lagenarium, pelo extrato aquoso de Eucalyptus citriodora
Elektroschlackeschmelzen von aluminothermischen hergestellten Titan-Aluminiumlegierungen - eine Alternative zum Kroll-Prozess?
Peter Heinrich Holthaus, weiland Conrector an der höhern Bürgerschule in Schwelm : eine Denkschrift
von F. W. M. HammerschmidtIn Fraktu
Elektroschlackeschmelzen von aluminothermischen hergestellten Titan-Aluminiumlegierungen - eine Alternative zum Kroll-Prozess?
Transformation of Arylmethylamines into α-Aminophosphonic Acids via Metalated Phosphoramidates: Rearrangement of Partly Configurationally Stable N-Phosphorylated α-Aminocarbanions
Enzyme in der organischen Chemie, 6. Mitt. [1]. Enantioselektive Hydrolysevon 1-Chloracetoxycycloalkylmethylphosphonaten mit Lipase AP 6 aus Aspergillus niger und chemoenzymatische Synthese chiraler nichtracemischer1-Aminocyclohexylmethylphosphonsaäuren
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