Glutamine residues

Figure 8.15 Sequence-specific protein-DNA interactions provide a general recognition signal for operator regions in 434 bacteriophage, (a) In this complex between 434 repressor fragment and a synthetic DNA there are two glutamine residues (28 and 29) at the beginning of the recognition helix in the helix-turn-helix motif that provide such interactions with the first three base pairs of the operator region.

Fig. 32 Transglutaminase (rGare)-mediated coupling between lysine and glutamine residues. Adapted with permission from Collier and Messersmith [72], Copyright 2003 American Chemical Society...

Figure 11.13 5-(Biotinamido)pentylamine can be used to label glutamine residues in proteins by enzymatic action of transglutaminase.

Figure 15. a) The active site of WT HIV protease complexed with A-76889, an inhibitor with a bulky P3 residue. Note the relatively spacious S3 pocket made possible by the presence of the small glycine and valine residues, b) The active site of WT FIV protease complexed with TL-3, an inhibitor with a small P3 residue. Note the relatively small constrained S3 pocket due to the presence of the relatively large isoleucine and glutamine residues. 

The mechanism of hydrolysis of cysteine peptidases, in particular cysteine endopeptidases (EC 3.4.22), shows similarities and differences with that of serine peptidases [2] [3a] [55 - 59]. Cysteine peptidases also form a covalent, ac-ylated intermediate, but here the attacking nucleophile is the SH group of a cysteine residue, or, rather, the deprotonated thiolate group. Like in serine hydrolases, the imidazole ring of a histidine residue activates the nucleophile, but there is a major difference, since here proton abstraction does not appear to be concerted with nucleophilic substitution but with formation of the stable thiolate-imidazolium ion pair. Presumably as a result of this specific activation of the nucleophile, a H-bond acceptor group like Glu or Asp as found in serine hydrolases is seldom present to complete a catalytic triad. For this reason, cysteine endopeptidases are considered to possess a catalytic dyad (i.e., Cys-S plus H-His+). The active site also contains an oxyanion hole where the terminal NH2 group of a glutamine residue plays a major role. 

Asparagine residues (and glutamine residues, see below) are sites of particular instability in peptides. As will be exemplified below, rates of degradation at asparagine residues are markedly faster (tenfold and even much more) than at aspartic acid residues. As reported, the tm values for the internal asparagine in a large number of pentapeptides ranged from 6 to 507 d under... 

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. 

As in the case of degradation at aspartic acid residues, the major structural factors that influence the reactivity of asparagine and glutamine residues... 

To illustrate some of the above points, the degradation of a few selected bioactive peptides containing asparagine and glutamine residues will be described. 

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