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Molecules, Cells, and Tissues

Amino Acids and Proteins (Section I)

Richard Brennan, Ph.D.
Jennifer Carbrey, Ph.D.

In all organisms, most proteins are made from the same 20 amino acid building
blocks yet proteins are quite diverse. Proteins are the most abundant biological
macromolecules and often function as enzymes, signaling molecules and receptors,
DNA-binding proteins and transcription regulators, and structural components. Proteins
are linear polymers of amino acids, the sequence of which is encoded by DNA. Strings
of amino acids fold into complex three-dimensional structures. The nature of the
structure determines the function of the protein. In addition, covalent modifications and
cofactors, molecules that participate in overall mechanisms of reaction, contribute to
protein function.
A global view of protein expression can be useful to determine the physiological
state of a cell. The proteome refers to all of the proteins that are expressed in a certain
population of cells under certain conditions. The metabolome, or the products of
metabolism that are present, indicate the enzymes that are active under certain
conditions. These tools can be powerful but they are constrained based on limits of
protein detection. The overall goal of identifying which proteins are expressed and
functional is to combine this information with biochemical and biophysical experiments
to determine the map of functional pathways in the biological system.

Amino Acids
Proteins are built from
amino acids, which are
organic acids and organic
amines. Each of the 20
amino acids has a backbone
of a carbon (the alpha
carbon) bound to an amine
group, a carboxylic acid
group, and an amino acid
Figure 1. The L and D isomers of Alanine. The side
specific group, called the side
chain specific to alanine is in red.
chain (Figure 1). Since the
alpha carbon is bound to 4 different groups, amino acids are chiral molecules. The
isomers of amino acids have the same chemical composition but the arrangement of the
four groups around the alpha carbon differs (Figure 1). Although two isomers exist for
each amino acid, only left-handed (L) amino acids are found in proteins.
The backbone and the side chains of amino acids both make important
contributions to protein structure. The amine, carboxylic acid, and alpha carbon that
make up the backbone are important for the polymerization of amino acids into a chain.
The side chains give proteins their sequence specific properties that affect the structure
and thus the function of the protein.

Molecules, Cells, and Tissues

Because amino acids have

an amino group and an
acidic group, their charge
differs when pH changes. In
amino acids that do not
have charged side chains,
at low pH both the amino
group and the acidic group
are protonated and have a
net charge of +1. At neutral
pH, the amino group is
protonated but the acidic
group is deprotonated. The
net charge is zero, but there
Figure 2. The concentration of different forms of an amino are two opposing charges
acid during changes in pH.
making the molecule a
zwitterion. At basic pH
both groups are deprotonated and the amino acid has a negative charge (Figure 2). At
physiological pH, amino acids are in their zwitterionic forms.
Amino acids can be grouped based on the chemical properties of their side
chains. The aliphatic amino acids have nonpolar side chains made of carbon chains (or
just hydrogen in the case of glycine) (Figure 3). Proline is a unique aliphatic amino acid
because the aliphatic chain is attached to its amide group making a 5-member ring. The
polar amino acids have uncharged groups that have dipole moments such as hydroxyls,
sulfhydryls, and amide carboxylate groups (Figure 3). Three amino acids have aromatic
side groups (Figure 4). Some amino acids have charged side chains either negative
or positive. Histidine contains a protonated side chain that can lose its proton at
physiological pH (Figure 4).

Figure 3. Side chains of aliphatic and polar amino acids.

Molecules, Cells, and Tissues

Negatively charged R groups

Figure 4. Aromatic, positively charged, and negatively charged amino acids.

Peptide bonds
The bonds that amino acids form to make a peptide or protein are peptide bonds.
Energy is used by the ribosome in a condensation reaction that eliminates water and
connects the nitrogen of the amino
group and the carbon of the carboxylic
acid (Figure 5). Since amino acids
have distinct ends, so do proteins. By
convention, the beginning of a protein
is the amino acid with the amino group
exposed. The end of the protein is the
portion with the amino acid with the
carboxylate exposed (Figure 5). The
nitrogen to carbon bond in peptide
Figure 5. The Amino and Carboxyl-terminal ends bonds is shorter than normal, which
of a peptide. Peptide bonds are highlighted with means it is a tighter bond that has
characteristics of a partial double
bond. The bond is tight enough to
make the peptide bond planar and to
restrict the rotation around it. This means that chains of amino acids are restricted to
rotation at phi and psi (Figure 6). Since these are the bonds on each side of the alpha
carbon with the side group, it is the side groups and their interactions that determine
how flexible an amino acid is at phi and psi.

Molecules, Cells, and Tissues

Post-translation modification of amino acids occurs

after they have been incorporated into the protein.
These modifications bind the side chains and change
the chemical properties of the amino acids. For
instance the sulfhydryl groups from two cysteine
residues can be oxidized to form a disulfide bond
between the two cysteine residues. Phosphorylation of
serine, threonine, tyrosine and histidine amino acids is
an important way for proteins to send signals.
Glycosylation adds sugar residues to amino acids that
are important on the surface of cells. Methylation of
nucleosomes bound to DNA changes gene
expression. Hydroxylation of certain amino acids is
important for connective tissue protein assembly.
Finally, addition of certain lipid molecules can target
proteins to the plasma membrane.

Figure 6. Phi and psi angles

of amino acids.

Amino acid chains of different lengths have different

names. Oligopeptide refers to chains of only a few
amino acids. Polypeptides contain many amino acids.
Chains of greater than 40 amino acids are referred to
as proteins. Most enzymes that catalyze chemical
reactions are proteins of greater than 100 amino acids.