Leucine analogs

N-methyl-N -nitro-N-nitrosoguanidine. Also, a strain that grew well on the leucine analog, 4-azaleucine was isolated. 

In an attempt to obtain mutants in E. coli resembling the leu S mutants of S. typhimurium, Dwyer tested several leucine analogs as growth inhibitors. While trifluoroleucine was not a very effective inhibitor, azaleucine (a-amino-jS-dimethylaminopropionic acid) was effective [26]. Resistant mutants were obtained and their characteristics... 

Figure 30-19. The analogous first three reactions in the catabolism of leucine, valine, and isoleucine. Note also the analogy of reactions and to reactions of the catabolism of fatty acids (see Figure 22-3). The analogy to fatty acid catabolism continues, as shown in subsequent figures.

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

Their studies involved the partial polymerization of NCAs of mixtures of specific amino adds having known e.e.s, followed by determination of the e.e.s of the amino adds in both the resulting polypeptides and in the residual unreacted NCA monomers. [94] In a typical experiment it was found that when an optically impure leucine NCA monomer having an l > d e.e. of 31.2% was polymerized to the extent of 52 % to the helical polyleucine peptide, the e.e. of the polymer was enhanced to 45.4 %, an increase of 14.2 %. In the same experiment the e.e. of the unreacted leucine NCA monomer was depleted to a similar extent. Analogous experiments with valine NCAs of known e.e.s, however, led to a reverse effect, namely, the preferential incorporation of the racemate rather than one enantiomer into the growing polyvaline peptide. This finding was interpreted to be the result of the fact that polyvaline consists of (3-sheets rather than a-helices, emphasizing that the Wald mechanism applies only to a-helix polymers. At about the same time Brach and Spach [95] showed that, under proper conditions, (3-sheet polymers could also be implicated in the amplification of amino add e.e.s. 

In the case of the influence of adjacent residues, there are clear mechanistic analogies between activation of aspartic acid (Sect. 6.3.3.2) and asparagine sites. The presence of a C-flanking glycine residue consistently increases deamidation of peptides, for the reasons discussed in Sect. 6.3.3.2 [6], Replacement of glycine with a more bulky residue such as valine, leucine, or proline can decrease reactivity more than tenfold [99]. 

Yeast isopropylmalate isomerase of the leucine biosynthetic pathway, which catalyzes a totally analogous reaction to that of aconitase, converts 3-hydroxy-3-carboxy-4-methylpentanoate to 2-hydroxy-3-carboxy-4-methylpentanoate via an allylic intermediate. In its initial characterization by EPR spectroscopy, a high-field shift in its EPR signal from a g-average of 1.96 to 1.90 is seen upon addition of substrate (70). This result suggests that its mechanism is the same as that found for aconitase. 

The stability of peptides is generally increased when natural amino acids are substituted by fluorinated analogs (e.g., tri- or hexafluoroleucine, hexafluorova-line). Such stabilization augments with the number of hexafluoroleucine residues introduced [77]. Native-like structure was preserved, but the peptides had a more structured backbone and less fluid hydrophobic core. Substitution of four leucine residues by trifluoroleucines in the leucine zipper peptide GCN4-p1d led to a substantial gain in thermal stability and resistance to chemical denaturation of the... 

The leucine zipper itself does not participate in the recognition it is only utilized for dimerization of the proteins. The N-terminal end of the basic leucine zipper motif is relatively unstructured in the absence of DNA. A helical structure is induced upon binding to DNA allowing specific contacts to the recognition sequence. Dimer formation is a prerequisite for the exact positioning of the N-terminal basic end in the major groove of the DNA. Analogous to the dimeric structure of the protein, the DNA sequence displays 2-fold synunetry (see 1.2.4). 

Parallel Pathways for Amino Acid and Fatty Acid Degradation The carbon skeleton of leucine is degraded by a series of reactions closely analogous to those of the citric acid cycle and j8 oxidation. For each reaction, (a) through (f), indicate its type, provide an analogous example from the citric acid cycle or /3-oxidation pathway (where possible), and note any necessary cofactors. 

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