L-Amino acids in proteins

TThe primary function of D-amino acid oxidase, present at high levels in the kidney, is thought to be the detoxification of ingested D-amino acids derived from bacterial cell walls and from cooked foodstuffs (heat causes some spontaneous racemization of the l-amino acids in proteins). Oxalate, whether obtained in foods or produced enzymatically in the kidneys, has medical significance. Crystals of calcium oxalate account for up to 75% of all kidney stones. ... 

The L amino acids in proteins, the D carbohydrates, the nucleic acids, aU are found to be homochiral, as observed as a single enantiomer. When the opposite enantiomers are found in biology, they are used for different functions, such as the D amino acids in some bacterial cell walls. Ordinary chemical reactions that create a new chiral center from optically inactive precursors normally produce a racemic mixture unless some chiral catalyst is present to direct the process. How did it get started before chiral catalysts such as enzymes were present ... 

Amino acids (except for glycine) contain a chiral centre (C. ) and are intrinsically optically active. Predominantly L-amino acids in protein, with no racemizalion during (gentle) hydrolysis. 

The deterruination of amino acids in proteins requires pretreatment by either acid or alkaline hydrolysis. However, L-tryptophan is decomposed by acid, and the racemi2ation of several amino acids takes place during alkaline hydrolysis. Moreover, it is very difficult to confirm the presence of cysteine in either case. The use of methanesulfonic acid (18) and mercaptoethanesulfonic acid (19) as the protein hydroly2ing reagent to prevent decomposition of L-tryptophan and L-cysteine is recommended. En2ymatic hydrolysis of proteins has been studied (20). 

The predominance of L-amino acids in biological systems is one of life s most intriguing features. Prebiotic syntheses of amino acids would be expected to produce equal amounts of L- and D-enantiomers. Some kind of enantiomeric selection process must have intervened to select L-amino acids over their D-connterparts as the constituents of proteins. Was it random chance that chose L- over D-isomers ... 

Racemization of the native L-amino acid in peptides and proteins to the D-enantiomer generally results... 

Amino acids are the building blocks of protein. Except for glycine, all amino acids come into two different chiral forms, laevorotatory (L) and dextrorotatory (D) these forms are called enantiomers. In living organisms, the amino acids in protein are almost exclusively... 

A.J. Link, M.L. Mock, D.A. Tirrell, Non-canonical amino acids in protein engineering, Curr. Opin. Biotechnol. 14(6) (2003) 603-609. 

In living organisms, chiral molecules are usually present in only one of their chiral forms. For example, the amino acids in proteins occur only as their l isomers glucose occurs only as its D isomer. (The conventions for naming stereoisomers of the amino acids are described in Chapter 3 those for sugars, in Chapter 7 the RS system, described above, is the most useful for some biomolecules.) In contrast, when a compound with an asymmetric carbon atom is chemically synthesized in the laboratory, the reaction usually pro-... 

L. N. Mackey, T. A. Beck, Quantitative high-performance liquid chromatographic determination of sulfur amino acids in protein hydrolysates, J. Chromatogr., 240 (1982), 455-461. 

Slupsky, C.M., Gentile, L.N., and McIntosh, L.P. (1998) Assigning the NMR spectra of aromatic amino acids in proteins analysis of two Ets pointed domains, Biochemistry and Cell Biology 76,379-390... 

The Pauling-Corey alpha helix. In addition to the right-handed helix shown, a left-handed one is also possible (with the same t-amino acids). In proteins, the helix always seems to be right-handed. [Reprinted by permission from L. Pauling, The Nature of the Chemical Bond, p. 500, Cornell Univ. Press, Ithaca, NY I960).]... 

Figure 25-2 Left-handed and right-handed a helices. The R and H groups on the < -carbon atom are in the correct position corresponding to the known configuration of the i-amino acids in proteins. (From Pauling, L., and Corey. R. B. unpublished drawings.)...

G6. Gehrke, C. W., Roach, D., Zumwalt, R. W., Stalling, D. L., and Wall, L. L., Quantitative Gas-Liquid Chromatography of Amino Acids in Proteins and Biological Substances. Anal. Biochem. Lab., Columbia, Missouri, 1968. 

Almost all of the naturally occurring amino acids in proteins are L-a-amino acids. The principal 20 amino acids in... 

Only L amino acids are constituents of proteins. For almost all amino acids, the I, isomer has S (rather than R) absolute configuration (Figure 2.5). Although considerable effort has gone into understanding why amino acids in proteins have the L absolute configuration, no satisfactory explanation has been reached. It seems plausible that the selection of L over D was arbitrary but, once made, the selection was fixed early in evolutionary history. 

Bacteria with surface polypeptides composed of D-amino acids are resistant to degradation because the proteases, the enzymes that immune system cells use to degrade protein in foreign cells, can only catalyze the hydrolysis of peptide bonds between L-amino acids. In other words, the active sites of proteases are stereospecific, i.e., they can only effectively bind peptides composed of L-amino acids. 

Like all the other amino acids in proteins, the L isomer of alanine is exclusively used, though D-alanine can be found as a component of bacterial cell walls. Another variant of alanine, called / -alanine, has the amino group on the carbon and is found in pantothenic acid. Alanine can be formed by transamination of pyruvate and thus has close links to pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. 

Isomers that result from different arrangements of four different groups around the same carbon atom represent another class of stereoisomers called optical isomers. Optical isomers have the same physical and chemical properties, except in chemical reactions where chirality is important, such as enzyme-catalyzed reactions in biological systems. Human cells, for example, incorporate only L-amino acids into proteins. Only the L-form of ascorbic acid is active as vitamin C. The chirality of a drug molecule can also be important. For example, only one isomer of some drugs is effective and the other isomer can be harmful. 

Figures 1.32 to 1.34 display the absorption, the first derivative and second derivative spectra of free L-phenylalanine, L-tyrosine and L-tryptophan in water, respectively. We notice important differences mainly in the second derivative spectra since the peaks and troughs positions differ in certain spectral ranges. For studies in proteins, since the three amino acids are bonded, comparative studies will be done not with L-amino acids in solution but with the N-acetyl amino acids derivative. However, before we go further in these comparative studies, let us see very briefly the origin of these derivative spectra.

The replacement of sulfur-containing amino acids in proteins by their selenium analogs has received some attention. For example, a variant of Escherichia coli was shown to indiscriminately incorporate selenium into its proteins l. In fact, the /8-galactosidase isolated from this system, which had 70-75% of its methionine residues replaced by the selenium analog, exhibited a virtually unaltered catalytic activity. Similarly, the indiscriminate incorporation of selenomethionine in proteins of the rat as well as E. coli suggests that the enzymes methionyl-tRNA synthetase and amino acid polymerase can accept both methionine and selenomethionine and their corresponding tRNA derivatives. There is some evidence which suggests that a similar phenomenon occurs with cysteine and selenocysteine ... 

Eyal, E., Chennnbhotla, C., Yang, L. W., and Bahar, I., Anisotropic fluctuations of amino acids in protein structures Insights from X-ray crystallography and elastic network models, Bioinformatics, 23,1175 (2007). 

Link, A. J., Mock, M. L., and Tirrell, D. A. Non-canonical amino acids in protein engineering. Current Opinion in Biotechnology 14, 603-609 (2003). 

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