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Protein structure

As discussed earlier, the shape of a protein is critical to its function. For example, an enzyme can bind to a specific substrate at a site known as the active site. If this active site is altered because of local changes or changes in overall protein structure, the enzyme may be unable to bind to the substrate. To understand how the protein gets its final shape or conformation, we need to understand the four levels of protein structure: primary, secondary, tertiary, and quaternary. For a short (4 minutes) introduction video on protein structure click here .

Primary structure

The unique sequence of amino acids in a polypeptide chain is its primary structure    . For example, the pancreatic hormone insulin has two polypeptide chains, A and B, and they are linked together by disulfide bonds. The N terminal amino acid of the A chain is glycine, whereas the C terminal amino acid is asparagine ( [link] ). The sequences of amino acids in the A and B chains are unique to insulin.

The amino acid sequences for the A chain and B chain of bovine insulin are shown. The A chain is 21 amino acids in length, and the B chain is 30 amino acids in length. One disulfide, or SS bond, connects two cysteine residues in the A chain. Two other disulfide linkages connect the A chain to the B chain.
Bovine serum insulin is a protein hormone made of two peptide chains, A (21 amino acids long) and B (30 amino acids long). In each chain, primary structure is indicated by three-letter abbreviations that represent the names of the amino acids in the order they are present. The amino acid cysteine (cys) has a sulfhydryl (SH) group as a side chain. Two sulfhydryl groups can react in the presence of oxygen to form a disulfide (S-S) bond. Two disulfide bonds connect the A and B chains together, and a third helps the A chain fold into the correct shape. Note that all disulfide bonds are the same length, but are drawn different sizes for clarity.

The unique sequence for every protein is ultimately determined by the gene encoding the protein. A change in nucleotide sequence of the gene’s coding region may lead to a different amino acid being added to the growing polypeptide chain, causing a change in protein structure and function. In sickle cell anemia, the hemoglobin β chain (a small portion of which is shown in [link] ) has a single amino acid substitution, causing a change in protein structure and function. Specifically, the amino acid glutamic acid is substituted by valine in the β chain. What is most remarkable to consider is that a hemoglobin molecule is made up of two alpha chains and two beta chains that each consist of about 150 amino acids. The molecule, therefore, has about 600 amino acids. The structural difference between a normal hemoglobin molecule and a sickle cell molecule—which dramatically decreases life expectancy—is a single amino acid of the 600. What is even more remarkable is that those 600 amino acids are encoded by three nucleotides each, and the mutation is caused by a single base change (point mutation), 1 in 1800 bases.

A portion of the hemoglobin amino acid sequence is shown. The normal hemoglobin beta chain has a glutamate at position six. The sickle cell beta chain has a valine at this position.
The beta chain of hemoglobin is 147 residues in length, yet a single amino acid substitution leads to sickle cell anemia. In normal hemoglobin, the amino acid at position seven is glutamate. In sickle cell hemoglobin, this glutamate is replaced by a valine.

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Source:  OpenStax, Cellular macromolecules: bis2a modules 3.0 to 3.5. OpenStax CNX. Jun 15, 2015 Download for free at https://legacy.cnx.org/content/col11827/1.1
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