Glycine G and proline P are unique in terms of chirality Gly is achiral and the conformational flexibility they confer upon the polypeptide chain that incorporates them. Proline could be considered to have a nonpolar character, so it is shown adjacent to the other amino acids with nonpolar hydrocarbon R groups - alanine A , isoleucine I , valine V , leucine L.
Cysteine C and methionine M are the two sulfur-containing amino acids; phenylalanine F , tyrosine Y and tryptophan W are aromatic; histidine H , lysine K and arginine R are basic and shown in order of increasing basicity. The acidic amino acids aspartate D and glutamate E , are shown together, along with their amides, asparagine N and glutamine Q.
By convention, a polypeptide sequence can be represented by the single letter symbol for an amino acid, with the first letter listed the amino end or at the N-terminus and the last letter listed the carboxy end or C-terminus. Glycine Gly, G is the simplest of the 20 naturally-occurring amino acids. As noted above, since R is just a hydrogen, glycine is the only natural amino acid that is not chiral at the alpha carbon.
Although in some classification schemes, glycine is considered nonpolar, hydrogen is so small that it contributes negligibly to nonpolar surface area.
Histidine His, H is one of the most interesting amino acids because of the variety of roles it can play in protein function, especially as a key residue in many enzyme active sites. Of all the ionizable side chains, the typical p K a of the imidazole ring of His is closest to a neutral pH. Studies of model compounds have established a range of 6. Neutral imidazole is a particularly good nucleophile, and histidine is one of the more reactive residues in proteins.
With a p K a near 7, the imidazole side chain is one of the strongest bases that can exist at neutral pH. In its neutral form, the imidazole side chain has an "ambidextrous" nature, since the nitrogen without a hydrogen is nucleophilic and can act as a hydrogen bond acceptor, while the nitrogen with the hydrogen bond is electrophilic and can act as a H-bond donor.
Protonation of a histidine residue inactivates it as a nucleophile. The protonated form of the imidazole ring is stabilized by resonance, by which the positive charge is shared by both nitrogen atoms of the ring. A prominent example of histidine as a crucial catalytic component in an enzyme mechanisms found in the serine proteases. Histidine is the central residue in a catalytic triad that is characteristic of this type of enzyme. A neutral imidazole acts as a base to enhance the power of serine as a nucleophile to attack the acyl carbon of a peptide bond to form a tetrahedral intermediate.
The protonated His residue in turn acts as a proton donor general acid to promote the loss of a leaving group from a tetrahedral intermediate. Cysteine Cys, C , one of two sulfur-containing amino acids, bears the most reactive side chain, a thiol -SH, also called sulfhydryl group attached to the beta carbon. The thiol is weakly acidic intrinsic p K a 9.
Both of these, particularly thiolate, are good nucleophiles, so the cysteine side chain can engage in many substitution reactions. Other reactions involve the oxidation of the thiol group.
The nucleophilic thiol group can be alkylated by reaction with alkyl halides or iodoacetate. Another common reaction, especially important one for cysteine's biological role in protein function, is the formation of a thioester linkage formally a carboxylic acid derivative. A disulfide bond is a covalent chemical bond between two sulfur atoms that can arise from the oxidative linking of two sulfhydryl thiol groups. This is a common theme for cysteine residues in proteins, especially those in oxidizing environments such as prevailing extracellular conditions.
The formation of disulfide bonds within proteins in vivo is a common example of a posttranslational modification. Shown at right are two cysteine residues in polypeptide chain s. The thiol groups are in their reduced forms in red in figure.
A disulfide-linked pair of cysteine residues is termed a cystine residue. The conversion of two sulfhydryl groups to a disulfide linkage is an oxidation reaction. Conversely, disulfide bonds can be reduced to yield two thiols, which is the reverse of the half-reaction shown at right.
The reduced thiols undergo a disulfide exchange reaction with disulfide-linked species. As has already been suggested, the intrinsic p K a values for ionizable groups are no guarantee that a particular residue in a particular protein will be in a particular ionization state at a pH consistent with its physiologically relevant structure and function.
Some p K a values are perturbed significantly from their intrinsic values, and these "anomalous" values are furthermore demonstrably important for the proper function of a protein in some cases. To illustrate the idea, consider an aspartate residue in a neutral pH 7 aqueous environment with a "normal" p K a. The residue will be overwhelmingly ionized. By plugging in values for the p K a of the residue, the pH of the medium, the Henderson-Hasselbalch equation can be used to calculate the proportion of ionized to unionized forms of the residue.
The top half of the figure below illustrates the situation. Now consider the influence of a nearby negative charge on the ionization of our hypothetical residue. The presence of the negative charge makes the ionization much less favorable, shifting the equilibrium to the left. The greater the shift in the equilibrium, the more the p K a is raised from its intrinsic value.
In the extreme case illustrated, the amounts of both forms of the residue are equal, and the p K a has been perturbed upward by three units.
An example of this effect where the residue with an anomalous p K a is directly involved in the protein's function is provided by lysozyme. Lysozyme is an enzyme produced by a variety of organisms that hydrolyzes the polysaccharide component of the peptidoglycan cell walls of many types of bacteria.
As the diagram below shows, the absolute configuration of the amino acids can be shown with the H pointed to the rear, the COOH groups pointing out to the left, the R group to the right, and the NH3 group upwards.
You can remember this with the mnemonic CORN. Why does Biochemistry still use D and L for sugars and amino acids? This explanation taken from the link below seems reasonable. These rules sometimes lead to absurd results when they are applied to biochemical molecules.
For example, as we have seen, all of the common amino acids are L, because they all have exactly the same structure, including the position of the R group if we just write the R group as R. However, they do not all have the same configuration in the R,S system: L-cysteine is also R -cysteine, but all the other L-amino acids are S , but this just reflects the human decision to give a sulphur atom higher priority than an oxygen atom, and does not reflect a real difference in configuration.
Worse problems can sometimes arise in substitution reactions: sometimes inversion of configuration can result in no change in the R or S prefix; and sometimes retention of configuration can result in a change of prefix.
It follows that it is not just conservatism or failure to understand the R,S system that causes biochemists to continue with D and L: it is just that the DL system fulfils their needs much better. As mentioned, chemists also use D and L when they are appropriate to their needs. The explanation given above of why the R,S system is little used in biochemistry is thus almost the exact opposite of reality. This system is actually the only practical way of unambiguously representing the stereochemistry of complicated molecules with several asymmetric centres, but it is inconvenient with regular series of molecules like amino acids and simple sugars.
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