12/14/2023 0 Comments Peptide backbone nitrogen atomThis can lead to myriad serious health problems such as breathlessness, dizziness, headaches, and abdominal pain for those affected by this disease. (credit: modification of work by Ed Uthman scale-bar data from Matt Russell)īecause of this change of one amino acid in the chain, hemoglobin molecules form long fibers that distort the biconcave, or disc-shaped, red blood cells and assume a crescent or “sickle” shape, which clogs arteries (Figure 3). In this blood smear, visualized at 535x magnification using bright field microscopy, sickle cells are crescent shaped, while normal cells are disc-shaped. 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.įigure 3. 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. The molecule, therefore, has about 600 amino acids. 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. Specifically, the amino acid glutamic acid is substituted by valine in the β chain. In sickle cell anemia, the hemoglobin β chain (a small portion of which is shown in Figure 2) has a single amino acid substitution, causing a change in protein structure and function. 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. The unique sequence for every protein is ultimately determined by the gene encoding the protein. In sickle cell hemoglobin, this glutamate is replaced by a valine. In normal hemoglobin, the amino acid at position seven is glutamate. The beta chain of hemoglobin is 147 residues in length, yet a single amino acid substitution leads to sickle cell anemia. Also note the first peptide chain possesses an internal loop.Figure 2. He found the primary structure to comprise of two chains linked by two cysteine disulfide bridges. This pioneering work, completed in 1953 after some 10 years of effort, earned a Nobel Prize for British biochemist Frederick Sanger (born 1918). Insulin was the first protein whose amino acid sequence was determined. Remember that reduction is the addition of hydrogen.Ĭysteine residues in the the peptide chain can form a loop buy forming the disulfide bond (-S-S-), while cysteine residues in different peptide chains can actually link what were otherwise separate chains. The reduction of a disulfide bond is the opposite reaction which again leads to two separate cysteine molecules. This is an important bond to recognize in protein tertiary structure. The sulfurs (yellow) join to make the disulfide bridge. An unspecified oxidizing agent (O) provides an oxygen which reacts with the hydrogen (red) on the -SH group to form water. The oxidation of two cysteine amino acids is shown in the graphic. The oxidation of two sulfhydryl groups results in the formation of a disulfide bond by the removal of two hydrogens. The amino acid cysteine undergoes oxidation and reduction reactions involving the -SH (sulfhydryl group). An important resonance contributor has a C=N double bond and a C-O single bond, with a separation of charge between the oxygen and the nitrogen.Īlthough B is a minor contributor due to the separation of charges, it is still very relevant in terms of peptide and protein structure – our proteins would simply not fold up properly if there was free rotation about the peptide C-N bond.ĭisulfide Bridges and Oxidation-Reduction This, along with the observation that the bonding around the peptide nitrogen has trigonal planar geometry, strongly suggests that the nitrogen is sp 2-hybridized. One of the most important examples of amide groups in nature is the ‘peptide bond’ that links amino acids to form polypeptides and proteins.Ĭritical to the structure of proteins is the fact that, although it is conventionally drawn as a single bond, the C-N bond in a peptide linkage has a significant barrier to rotation, almost as if it were a double bond. Resonance contributors for the peptide bondsĪ consideration of resonance contributors is crucial to any discussion of the amide functional group.
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