Asparagine formation

Min B, Pelaschier JT, Graham DE, Tumbula-Hansen D, Soil D. Transfer RNA-dependent amino acid biosynthesis an essential route to asparagine formation. Proc. Natl. Acad. Sci. U.S.A. 2002 99 2678-2683. 

L-Asparagine is a nonessential amino acid that can be synthesized by most mammahan cells, except for those of certain lymphoid human malignancies, which lack or have very low levels of the synthetase enzyme required for L-asparagine formation. L-Asparagine is degraded by the enzyme L-asparaginase, which depletes existing... 

Asparagine formation - Asparagine synthetase catalyzes the conversion of aspartate to... 

Coagulation Factors II, III, VII, IX, X, XI, and Xlla fragments, thrombin, and plasmin are classified as serine proteases because each possesses a serine residue with neighboring histidine and asparagine residues at its enzymatically active site (Table 3). Factors II, VII, IX, and X, Protein C, Protein S, and Protein Z are dependent on the presence of vitamin K [84-80-0] for their formation as biologically functionally active procoagulant glycoproteins. 

In contrast to AMPA receptors, NMDA receptor channels display a prominent Ca2+ permeability, which is largely independent ofthe subunit composition. It has been shown by mutational analysis that the Ca2+ permeability of recombinant NMDA receptors is dependent on a residue at a position equivalent to the Q/R site of AMPA subunits. Both NR1 and NR2 subunits contain an asparagine (N) residue at this position. Replacing this N with an R within the NR1 subunit led to the formation of NMDA receptors with a strongly reduced Ca2+ permeability, whereas exchanging N for Q in the NR2 subunit had only a small effect,... 

Tarr and Hibbert13 published the first detailed study of the formation of bacterial cellulose. A systematic series of experiments, conducted with a view to obtaining a culture medium which did not support visible growth of A. xylinum until a suitable source of carbon was added, indicated that a solution (pH 5.0) containing 0.1% asparagine, 0.5% potassium dihydrogen phosphate, 0.1% sodium chloride and 0.5% ethanol satisfied these requirements. Maximum polysaccharide formation oc-... 

DePace, A. H., Santoso, A., Hillner, P., and Weissman, J. S. (1998). A critical role for amino-terminal glutamine/asparagine repeats in the formation and propagation of a yeast prion. Cell 93, 1241-1252. 

Formation of the 2-Acetamido-2-deoxy-/ -D-glucosyl - L-Asparagine Linkage... 

C Ressler. Formation of a,Y-diaminobutyric acid from asparagine-containing peptides. J Am Chem Soc 78, 5956, 1956. 

Before doing so, we briefly examine the influence of conformation and flexibility. Indeed, formation of succinimide is limited in proteins due to conformational constraints, such that the optimal value of the and ip angles (Sect. 6.1.2) around the aspartic acid and asparagine residues should be +120° and -120°, respectively [99], These constraints often interfere with the reactivity of aspartic acid residues in proteins, but they can be alleviated to some extent by local backbone flexibility when it allows the reacting groups to approach each other and, so, favors the intramolecular reactions depicted in Fig. 6.27. When compared to the same sequence in more-flexible random coils, elements of well-formed secondary structure, especially a-helices and 13-turns, markedly reduce the rate of succinimide formation and other intramolecular reactions [90][100],... 

The most important degradation mechanism of asparagine and glutamine residues is formation of an intermediate succinimidyl peptide (6.63) without direct backbone cleavage (Fig. 6.29, Pathway e). The reaction, which occurs only in neutral and alkaline media, begins with a nucleophilic attack of the C-neighboring N-atom at the carbonyl C-atom of the Asn side chain (slow step). The succinimide ring epimerizes easily and opens by hydrolysis (fast step), as shown in Fig. 6.27, to yield the iso-aspartyl peptide (6.64) and the aspartyl peptide (6.65) in a ratio of 3 1. 

The influence of secondary structure on reactions of deamidation has been confirmed in a number of studies. Thus, deamidation was inversely proportional to the extent of a-helicity in model peptides [120], Similarly, a-hel-ices and /3-turns were found to stabilize asparagine residues against deamidation, whereas the effect of /3-sheets was unclear [114], The tertiary structure of proteins is also a major determinant of chemical stability, in particular against deamidation [121], on the basis of several factors such as the stabilization of elements of secondary structure and restrictions to local flexibility, as also discussed for the reactivity of aspartic acid residues (Sect. 6.3.3). Furthermore, deamidation is markedly decreased in regions of low polarity in the interior of proteins because the formation of cyclic imides (Fig. 6.29, Pathway e) is favored by deprotonation of the nucleophilic backbone N-atom, which is markedly reduced in solvents of low polarity [100][112],... 

A systematic study with two series of pentapeptides has afforded much information on the influence of flanking residues on asparagine reactivity [126]. In these two series, the central asparagine residue occurred in the sequences Val-Xaa-Asn-Ser-Val and Val-Ser-Asn-Xaa-Val, where Xaais one of ten different residues. In acidic solutions, the Asp peptide was the only product found, and its rate of formation was independent of the nature of the... 

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