Asparagine, Asp

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

Ala Alanine Arg Arginine Asn Asparagine Asp Aspartic Acid Cys Cysteine Gin Glutamine Glu Glutamic Acid Gly Glycine His Histidine lie Isoleucine... 

FIGURE 17.7 Some important direct interactions between conserved amino acid residues of the active site of influenza A virus sialidase and a-Neu5Ac. Ala, alanine Arg, arginine Asn, asparagine Asp, aspartic acid Glu, glutamic acid His, histidine lie, isoleucine Typ, tryptophan Tyr, tyrosine. 

AMP adenosine monophosphate cAMP cyclic AMP Arg arginine Asn asparagine Asp aspartate... 

Fig. 20. Primary structure of hen-egg lysozyme. ALA alanine, ARG arginine, ASN asparagine, ASP aspartic acid, CYS cysteine, GLN glutamine, GLU glutamic acid, GLY glycine, HIS histidine, ILE isoleucine, LEU leucine, LYS lysine, MET methionine, PHE phenylalanine, PRO proline, SER serine, THR threonine, TRP tryptophan, TYR tyrosine, VAL valine. (Redrawn from Canfield and Lu, 1965).

The following system of abbreviations for amino acids will be used Abu = L- <>-aminobutyric acid Ala = L-alaninei /3-Ala = /3-alanine Arg = L-arginine Asn = L-asparagine Asp = L-aspartic acid Cys = L-cysteine (or L-half cystine) Dbu = L-o y-diamino-butyric acid Gin - L-glutamine Glu = L-glutamic acid Gly = glycine His = L-histidine lie = L-isoleucine alle = L-allo-isoleucine Leu = L-leucine Lys = L-lysine ... 

Ala = alanine Asn = asparagine Asp = aspartic acid Gin = glutamine Glu = glutamic acid His = histidine He = isoleucine Leu = leucine Lys = lysine Met = methionine PDB = Brookhaven Protein Data Base Phe = phenylalanine rmsd = root mean square deviation SA = simulated annealing Val = valine. 

Ala—Alanine Arg—Arginine Asn—Asparagine Asp—Aspartic acid Cys—Cysteine... 

Until recently, the catalytic role of Asp ° in trypsin and the other serine proteases had been surmised on the basis of its proximity to His in structures obtained from X-ray diffraction studies, but it had never been demonstrated with certainty in physical or chemical studies. As can be seen in Figure 16.17, Asp ° is buried at the active site and is normally inaccessible to chemical modifying reagents. In 1987, however, Charles Craik, William Rutter, and their colleagues used site-directed mutagenesis (see Chapter 13) to prepare a mutant trypsin with an asparagine in place of Asp °. This mutant trypsin possessed a hydrolytic activity with ester substrates only 1/10,000 that of native trypsin, demonstrating that Asp ° is indeed essential for catalysis and that its ability to immobilize and orient His is crucial to the function of the catalytic triad. 

Figure 2.11 y-Carboxylation of glutamate residues (Glu) yields y-carboxyglutamate (Gla), whereas (3-hydroxy lation of aspartate (Asp) yields (3-hydroxyaspartate (Hya) and (3-hydroxylation of asparagine (Asn) yields 3-hydroxyasparagine (Hyn)... 

The simplest degradation displayed by asparagine and glutamine is direct hydrolytic deamidation of the side-chain carboxamido group (Fig. 6.29, Pathway d). Such a reaction, however, is seen only at low pH values, and its biological significance appears negligible. Its product is the Asp peptide (6.62) whose further reactions have been presented in Fig. 6.27. 

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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