Protein structure levels

Fig. 2 Illustration of protein structure levels. Shown are primary structure (amino acid sequence), secondary structure (local order of protein chain, a-helix shown as an example), tertiary structure (assembly of secondary structure elements), and quaternary structure (relationship of different protein chain in multisubunit protein). (From Ref. 66.)...

Besides these shifts which do not affect too strongly the HX results at the protein structure level, one can meet some more tricky cases with identical amino acid or elemental composition in completely different regions of the protein. This means that tandem MS is a mandatory step in the assignment of... 

Chapter 16, Amino Acids, Proteins, and Enzymes, discusses amino acids, formation of peptide bonds and proteins, structural levels of proteins, enzymes, and enzyme action. Amino acids are drawn as their ionized forms in physiological solutions. Section 16.3 describes the primary level of protein structure. Section 16.4 describes the secondary, tertiary, and quaternary levels of proteins. Enzymes are discussed as biological catalysts, along with the impact of inhibitors and dena-turation on enzyme action. 

Many proteins consist of two or more interacting polypeptide chains of characteristic tertiary structure, each of which is commonly referred to as a subunit of the protein. Subunit organization constitutes another level in the hierarchy of protein structure, defined as the protein s quaternary (4°) structure (Figure 5.10). Questions of quaternary structure address the various kinds of subunits within a protein molecule, the number of each, and the ways in which they interact with one another. 

Quaternary structure (Section 26.9) The highest level of protein structure, involving a specific aggregation of individual proteins into a larger cluster. 

FIGURE 1.4 Increasing levels of protein structure. A protein has a given amino acid sequence to make peptide chains. These adopt a 3D structure according to the free energy of the system. Receptor function can change with changes in tertiary or quaternary structure. 

Protein-protein interactions predicted on the sequence level can be studied in more detail on the structure level. Single Nucleotide Polymorphisms can be mapped on 3D structures of proteins in order to elucidate specific structural causes of disease. 

Figure 5.11 The four levels of protein structure. From Lehninger, A.L., Nelson, D. and Cox, M.M. Principles of Biochemistry, 3rd Edn, Worth Publishers, NJ, 2000, and reproduced with permission.

The cord that connects this computer to its keyboard illustrates the primary, secondary, and tertiary levels of protein structure. 

The essential distinction between the approaches used to formulate and evaluate proteins, compared with conventional low molecular weight drugs, lies in the need to maintain several levels of protein structure and the unique chemical and physical properties that these higher-order structures convey. Proteins are condensation polymers of amino acids, joined by peptide bonds. The levels of protein architecture are typically described in terms of the four orders of structure [23,24] depicted in Fig. 2. The primary structure refers to the sequence of amino acids and the location of any disulfide bonds. Secondary structure is derived from the steric relations of amino acid residues that are close to one another. The alpha-helix and beta-pleated sheet are examples of periodic secondary structure. Tertiary... 

Thus far we have concentrated on the primary structure (amino acid sequence) of a polypeptide. Higher level protein structure can be described at various levels, i.e. secondary, tertiary and quaternary ... 

Proteins differ greatly in their intrinsic susceptibility to proteolytic attack. Resistance to proteolysis seems to be dependent upon higher levels of protein structure (i.e. secondary and tertiary structure), as tight packing often shields susceptible peptide bonds from attack. Denaturation thus renders proteins very susceptible to proteolytic degradation. 

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