We tested the biological significance of two amino acid mutations in the PB2 protein (glutamic acid to lysine at position 627 and aspartic acid to asparagine at position 701) of A(H7N9) viruses for mammalian adaptation. Mutants were assessed for their viral polymerase activities, growth kinetics in mammalian and avian cells, and pathogenicity in mice. We found that lysine at position 627 and as...

An enzyme system that catalyzes the conversion of Laspartate-W to asparagine-W in the presence of glutamine, ATP, and Mg++ has been purified 108-fold from a homogenate of the Novikoff hepatoma. ATP is converted to adenosine 5’-phosphate and inorganic pyrophosphate, and substitution of hydroxylamine for glutamine yields P-aspartylhydroxamate. The data suggest that the synthesis of asparagine in ...

Asparaginase is widely used in chemotherapeutic regimens for the treatment of acute lymphoblastic leukemia (ALL) and has led to a substantial improvement in cure rates, especially in children. Optimal therapeutic effects depend on a complete and sustained depletion of serum asparagine. However, pronounced interpatient variability, differences in pharmacokinetic properties between asparaginases ...

The effect of Escherichia coli L-asparaginase on phytohemagglutinin (PHA)-induced transformation of human lymphocytes was studied. Transformation was remarkably suppressed by the enzyme when it was added to the cul ture not later than 24 hr after its initiation. The effective concentration was more than 0.2 i.u./tube. Guinea pig serum and L-0-aspartohydroxamic acid, an L-asparagine analog, have...

An enzyme that catalyzes the hydrolysis of both glutamine and asparagine has been purified to homogeneity from extracts of Pseudomonas acidovorans. The enzyme having a ratio of glutaminase to asparaginase of 1.45:1.0 can be purified by a relatively simple procedure and is stable upon storage. The glutaminase-asparaginase has a relatively high affinity for L-asparagine (Km=1.5 X 10(-5) M) and L-...

Protoplasts isolated from young and mature pea leaves (Pisum sativum L.) were broken and their contents fractionated by differential centrifugation or on sucrose-density gradients. Asparaginase was found only in the cytosol of young leaves. Asparagine aminotransferase was found in both young and mature leaves and was localized exclusively in the peroxisome. This corroborates the observation tha...

It is widely accepted that ubiquitin-conjugating enzymes contain an active site asparagine that serves as an oxyanion hole, thereby stabilizing a negatively charged transition state intermediate and promoting ubiquitin transfer. Using structural and biochemical approaches to study the role of the conserved asparagine to ubiquitin conjugation by Ubc13-Mms2, we conclude that the importance of thi...

Successful chemotherapeutic treatment of drug-responsive cancers can be compromised by the acquisition of drug resistance. Standard remission induction therapy for childhood acute lymphoblastic leukemia includes L-asparaginase, since the leukemic cells lack asparagine synthetase (AS) activity and require exogenous asparagine. We have used the Chinese hamster ovary cell line N3, which lacks AS a...