Chemical structures amino-acid side chains

Proteins are the indispensable agents of biological function, and amino acids are the building blocks of proteins. The stunning diversity of the thousands of proteins found in nature arises from the intrinsic properties of only 20 commonly occurring amino acids. These features include (1) the capacity to polymerize, (2) novel acid-base properties, (3) varied structure and chemical functionality in the amino acid side chains, and (4) chirality. This chapter describes each of these properties, laying a foundation for discussions of protein structure (Chapters 5 and 6), enzyme function (Chapters 14-16), and many other subjects in later chapters. 

The DQFCOSY spectrum of RpII in D O is shown in Figure 2. Each cross peak in this spectrum identifies a pair of coupled spins of the amino acid side chains. Since couplings are not propagated efficiently across amide bonds, all groups of coupled spins occur within individual amino acids. The chemical structure of an amino acid side chain is reflected in the characteristic coupling network and chemical shifts (13). Valine spin system (CH-CH-(CH3)2) explicitly shown in Figure 2 as an example. 

Solid state 13C CPMAS NMR spectra of Wheat High Molecular Weight (W.HMW) subunits show well resolved resonances identical with spectra of dry protein and peptide samples [24], Most of the amino acids side-chain resonances are found in the 0-35 ppm region followed by the alpha resonances of the most abundant amino acids glycine, glutamine and proline at chemical shifts of 42, 52 and 60 ppm, respectively, and the carbonyl carbons show a broad peak in 172-177 ppm region. The CPMAS spectra of hydrated whole HMW provides important information on the structural characteristics. 

The precise chemical interactions between an adhesin and its receptor are also important. For example, direct- and water-mediated hydrogen bonds are the most important interactions within the carbohydrate-recognition domain in carbohydrate-binding adhesins on the host cell surface (Weis and Drickamer, 1996). Nonpolar van der Waals interactions and hydrophobic "stacking of the receptor oligosaccharide rings with aromatic amino acid side chains of the bacterial adhesin protein also contribute to oligosaccharide-protein interactions. X-ray structural... 

Figure 8 Summary of chain release strategies utilized by NRPS assemblies. The terminal domains involved in the chemistry are illustrated. The domain abbreviations are defined in the text, in general, for chemical structures, R and R represent peptide components and R" represents various amino acid side chains.

Figure 16 (a) Structures of adenylation domain intermediates and inhibitors aminoacyl-sulfamoyl adenosine (AMS) and cisoid -like macrocyclic inhibitor, (b) Alkyne-functionalized chemical probe for NRPS A and PCP domains, (c) Structure of aminoacyl PCP, SNAC substrate analogue, and hydrolytically stable phosphopantetheinyl analogue, (d) Structure of vinylsulfonamide probe. R represents a peptide component and R an amino acid side chain. 

The amino acids that are included in the genetic code (see p.248) are described as proteinogenic. With a few exceptions (see p. 58), only these amino acids can be incorporated into proteins through translation. Only the side chains of the 20 proteinogenic amino acids are shown here. Their classification is based on the chemical structure of the side chains, on the one hand, and on their polarity on the other (see p. 6). The literature includes several slightly different systems for classifying amino acids, and details may differ from those in the system used here. 

Piperazines and derivatives are archaetypical scaffolds and can be considered as efficient, however, structurally simple peptidomimics. The scaffolds combine conformational rigidity with peptide-like spacial placement of amino acid side chains or isosteres thereof. Moreover, piperazines can be used to confine compounds with beneficial properties such as water solubihty. Piperazines are therefore in the center of synthetic interest and many different synthetic pathways have been designed [16-19]. A preferred way to synthesize different piperazine scaffolds with plenty of variabihty provides MCR chemistry. Several piperazine scaffolds are currently only accessible by isocyanide-based MCR. Likely they could be assembled by sequential synthesis as well however, the synthetic efficiency, the diversity, and the size of the alternative chemical space will be inferior. The application of... 

The chemical modification studies have thus not yet led to a much more conclusive picture of the active site than that outlined in Fig. 12, and the identification of amino acid side chains involved in catalysis or substrate binding may have to await the completion of the crystal structure determination. The reporter properties of the Co(II) enzyme clearly show, however, that an open coordination position is of decisive functional importance, that the metal ion is intimately associated with the basic group participating in the reaction, and that the metal ion is probably also involved in the binding of one of the substrates, HCO3. 

All living organisms are chemical factories, and virtually every chemical reaction that occurs in a living system is catalyzed by special proteins called enzymes. All enzymes are globular proteins. Folding the peptide chains into a compact structure creates a chiral pocket. This is called the active site of the enzyme. The extraordinary specificity that enzymes show for their given substrate molecules is because the active site exactly matches the dimension and shape of the molecules upon which the enzyme acts. One reason enzymes speed reaction rates is that enzymes capture reacting molecules and hold them in place next to each other. Furthermore, key amino acid side chains are located in the active site of each enzyme. For example, if a reaction is catalyzed by acid, then an acidic side chain will be located in the active site, exactly where it is needed to catalyze the reaction. 

A large number of chemical and physical properties, manifest in the amino acid side chains, have been thoroughly examined by many investigators. Attempts have been made to correlate these properties with their relatedness among protein sequences. What is most relevant is how these side chains interact with the backbone and with one another and what roles they each play within particular types of secondary and tertiary structure. The parametric description of residue environments with the help of solvent accessibility, secondary structure, backbone torsion angles, pairwise residue-residue distances, or Ca positions is the comparison between amino acid types at protein sequence positions and residue locations in structural templates. A recent review has evaluated and quantified the extent to which the amino acid type-specific distributions of commonly used environment parameters discriminate with respect to the 20 amino acid types (Sunyaev et al., 1998). Some of the important amino acid properties and residue environments are discussed below. 

---