Protein Structure

Fig.1 The 20 fundamental α-amino acids that are the
building blocks for proteins. (Blass, 2015)

As the absolute majority of drug targets applied in clinic treatment, proteins are the tools that give rise to most biological functions. Their remarkable scope of functions includes mechanical support, reaction catalysis, nerve impulse transmission, cell growth and differentiation, transport and storage, and coordination of movement. Proteins are involved in virtually all the bioactivities that support life. While there are substantial differences between the various types of proteins, there are also several similarities that should be considered. Therefore, a clear explanation of the structure of proteins as drug targets is important to reveal the mechanism of drug-target interaction and develop novel target proteins. As a world-leading company in the field of protein engineering, Creative Biolabs has rich experience and established platforms in protein research including new drug targets discovery.

Primary Structure of Proteins

First and foremost, the structure of all proteins is built upon a small set of α-amino acids linked together through a series of amide bonds. Nature proteins rely primarily on a set of 20 amino acids while some unusual amino acids have been found in some species. The α-amino acids are linked together through a series of amide bonds to form linear polypeptide chains that can contain from a few dozen α-amino acids to thousands.

Three-Dimensional Structures of Proteins

Proteins have distinct three-dimensional shapes that are dictated by their primary structure and through a variety of different types of physicochemical interactions that occur within the framework of the protein itself. The spatial arrangements created by amino acids that are close to one another in a linear sequence are referred to as the secondary structure of the protein. The combination of the secondary structures is referred to as the tertiary structure of a protein, while the organization of the subunits into the functional units and the nature of their contacts are referred to as the quaternary structure. However, a quaternary structure is not necessary to perform a biological function in some cases.

Fig.2 The four levels of protein structure. (Joosten, 2010)

Interactions in Protein Structures

The physicochemical interactions that occur within a protein framework can be classified into one of several groups: covalent bonding, electrostatic interactions, and non-covalent interactions. Although covalent bonds such as disulfide bridge and electrostatic interactions, which was referred to as salt bridges, are strong interaction providing support for the secondary and tertiary structure of proteins, they are not the predominant force to form the protein structure. Non-covalent interactions, such as hydrophobic interactions, π-stacking, π-cation interactions, and hydrogen bonding, are regarded as the major drivers of protein folding.

Fig.3 Typical interactions in protein structures. (Blass, 2015)

As a basis for drug discovery, protein structures analysis is important to screen the potential novel targets and clarify the functions of disease-related proteins. As an advanced services provider, Creative Biolabs launched various protein research services based on our established platforms. If you are interested in drug target development or other fields in protein engineering, please feel free to contact us.

References

1. Blass, B. E. Basic principles of drug discovery and development. Elsevier. 2015.
2. Joosten, R. P. X-Ray structure re-refinement. Combining old data with new methods for better structural bioinformatics. SI:sn. 2010.