Amino acids, proteins and enzymes

In a nutshell

Proteins are polymers made from amino acids. They are formed via a condensation reaction where the amino acids are joined together by a peptide link. A protein consists of four structural levels which are, primary, secondary, tertiary and quaternary structures. Enzymes are highly specific proteins which act as a biological catalyst. The active site of enzymes may be blocked by competitive inhibitors. Some drugs are inhibitors. 

Proteins

Proteins are polymers made up of monomers known as amino acids. Two amino acids join together to form a dipeptide. A chain of amino acids is known as a polypeptide. Proteins are the assembly of two or more polypeptide chains. 

Amino acid structure

All $$2$$-amino acids have the same general structure. They each have a carboxyl group (-$$COOH$$), an amino group (-$$NH_2$$), a hydrogen atom and a variable group represented by R. 

Condensation reactions

Polypeptides are formed via a condensation reaction where amino acids join together by the means of a peptide link. The reverse reaction is called hydrolysis, which happens when a polypeptide is broken down (e.g., during digestion) and requires a molecule of water. 

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Protein structure

Proteins are macromolecules. Their structures can be divided into four levels. These levels are known as primary, secondary, tertiary and quaternary structures. 

Primary structure

The sequence of amino acids in a polypeptide chain. It is specific for each polypeptide/protein.

Example

Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val

Example

Secondary structure

Hydrogen bonds form between carboxyl and amino groups in neighbouring amino acids. This makes the protein coil into a secondary structure known as an $$\alpha$$-helix or fold into a $$\beta$$-pleated sheet. An $$\alpha$$-helix arises when hydrogen bonds form between every fourth peptide bond and a $$\beta$$-pleated sheet occurs when proteins fold in a way that causes two parts of the polypeptide to be parallel to each other. This allows the parallel amino acids to form hydrogen bonds. Fibrous proteins such as collagen and keratin have secondary structures.

Tertiary structure

The tertiary structure is where the protein adopts a $$3D$$ structure. The coiled chain of amino acids is coiled and/or folded further. This allows more bonds to form between different amino acids. 

The tertiary structure determines the function of a protein. It is very specific to the role a protein carries out. Changes in pH and temperature can lead to a change in the tertiary structure. As a consequence, the polypeptide chain or protein may not function well or may denature.

Quaternary structure

Proteins made up of two or more polypeptide chains have a quaternary structure. Each chain in the quaternary structure makes up one subunit of the protein. 

Example

Haemoglobin 

Protein structure summarised

Enzymes

Enzymes are soluble, globular proteins. However, they may have non-protein components called cofactors or prosthetic groups. They are biological catalysts as they increase the rate of chemical reactions by reducing the activation energy. They also catalyse metabolic reactions in living organisms.

Enzyme specificity

Enzymes are highly specific due to the precise nature of the tertiary structure and especially the active site. The active site is where the action occurs. It is a small region in the enzyme with a specific shape. The substrate binds to the active site and is converted into the products required. The active site accommodates molecules which are complementary to the shape of the active site. The binding of particular molecules (substrates) to the active site is known as the lock and key model.

As enzymes are made up of amino acids, it is no surprise that they contain chiral centres. This is what makes their active site stereospecific. This means only one of the enantiomers will fit into the active site.

Competitive inhibitors

Competitive inhibitors are molecules with a similar shape to a substrate and they may block the active site. This prevents the formation of an enzyme-substrate complex and for the desired reaction to occur. 

The frequency of inhibition is dependant upon the relative concentrations of the substrate and the inhibitor and the affinity of the inhibitor for the active site. A greater concentration of inhibitors compared to the concentration of substrate will lead to the majority of the active site to be occupied by the inhibitors. 

Drugs

Some drugs act as inhibitors by blocking the active site.

Example

Some antibiotics block the active site of enzymes which help build bacterial cell walls. The prevention of the enzyme being able to carry out its function leads to the weakening of the bacterial cell wall and the bacteria eventually dies.

Since enzymes (including their active site) can be stereospecific, time, energy and specialism is required to identify a drug molecule which fits into the active site. This includes identifying the enantiomer if the molecule is chiral.

A lengthy process of trial and error is usually the means of identifying new drugs. Experiments are carried out to help identify potential inhibitors. The results are then analysed to determine what may need to be remodelled or modified. Technology and advanced instruments can be used to model the shape of an active site. This allows researchers to predict the potential interaction between the active site and the inhibitor, saving resources and labour. A number of potential inhibitors can be investigated to see which one will be suitable before being synthesised and trialled in labs.