In most cases, mutations in the core of a protein that replace a smaller nonpolar side chain in the wild-type (e.g., Ala, Val) with a larger nonpolar side chain (e.g., Leu, Ile, Phe, Trp) in the mutant, result in significant destabilization and misfolding of the mutant. What feature of the protein core explains this observation? Why would such a mutation prevent a protein from folding properly?

In most cases, mutations in the core of a protein that replace a smaller nonpolar side chain in the wild-type (e.g., Ala, Val) with a larger nonpolar side chain (e.g., Leu, Ile, Phe, Trp) in the mutant, result in significant destabilization and misfolding of the mutant. What feature of the protein core explains this observation? Why would such a mutation prevent a protein from folding properly?

Human Heredity: Principles and Issues (MindTap Course List)

11th Edition

ISBN:9781305251052

Author:Michael Cummings

Publisher:Michael Cummings

Chapter10: From Proteins To Phenotypes

Section: Chapter Questions

Problem 20QP: If an extra nucleotide is inserted in the first exon of the beta globin gene, what effect will it...

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The following is a portion of a protein: met-trp-tyr-arg-gly-pro-thr-Various mutant forms of this protein have been recovered. Using the normal and mutant sequences, determine the DNA and mRNA sequences that code for this portion of the protein, and explain each of the mutations. a. met-trp- b. met-cys-ile-val-val-leu-gln- c. met-trp-tyr-arg-ser-pro-thr- d. met-trp-tyr-arg-gly-ala-val-ile-ser-pro-thr-
Why would the mutation Ile -> Asp be likely to destabilize a protein? Why would the mutation Ile ->Val be likely to destabilize a protein? Why would the mutation Val -> Ile be likely to destabilize a protein?
Imagine a globular protein with a histidine that is involved in a salt bridge to an aspartic acid, in an internal (hydrophobic) region of the protein. What would happen to the pKa of that histidine R group if the protein was mutated, and the aspartic acid was replaced with an alanine? (i.e., would the pKa increase, decrease, or stay the same?). Assume that the location of the histidine stays the same. Explain your answer clearly
On average, how many phosphoanhydride bonds (P;-P; bonds) are directly hydrolyzed in thecourse of synthesizing a 200 amino acid protein? Assume that you begin with the mature mRNA,ribosomal subunits, tRNAs, free amino acids, and all necessary factors.
To better understand the effects of palmitoylation on protein X, researchers want to chemically attach a palmitic acid at a specific position in this protein. The researchers first try to feed cells with palmitic acid or an amino acid with a C16 side chain. Neither of the initial experiments is successful in helping the researchers learn more about the biological role of palmitoylated protein X. Why? Suggest a strategy to specifically incorporate a palmitoylation site into protein X.
Consider the peptide Asp-Lys-Phe-Glu-Asn-Tyr-Gln-Val-Cys. In a single beaker, you treat this peptide with 2 proteases. One protease cleaves at the N-terminus of aromatic R groups and the other cleaves at the C-terminus of polar, non-ionizable R groups. Following the enzymatic digestion, you want to separate your peptide fragments so that you can identify them. You choose to separate the fragments using an anion exchange column. Beginning at pH=6 you apply your peptide fragments to the column and you gradually decrease the pH of the column stopping the separation when the pH of the column equals 4. Omitting chemical structures, write the amino acid sequence of the peptide fragments that are produced from this digest. Write the order that these fragments will elute from the column (if at all). (Relevant pKa values are: 2.1, 3.8, 4.3, 8.3, 9.6, 10.1, and 10.5)
Q) a) A protein gains a mutation of a surface exposed residue. The mutation is Arg --> Leu. Based on the sequence of the protein when it folds the Leu remains on the surface of the protein. What is the change in chemical characteristic of the amino acid caused by this mutation? b) Briefly explain any entropic consequences of this mutation. (2 sentences MAX) c) What might happen in order to overcome these entropic consequences and how would that affect the cell? (1-2 sentences)
This problem concerns a "typical" tyrosine residue found on the surface of a globular protein. a) If the pKa of this residue is 10.1, at what pH will this residue be found in its deprotonated state in 99% of protein molecules? b) How would the presence of a neighboring negatively charged residue effect the equilibrium expression for the dissociation of tyrosine? c) Would the presence of the negatively charged residue raise or lower the pKa of this tyrosine? Justify and/or explain your answers in 1–2 sentences each for parts b) and c).
Consider a short peptide that forms an alpha-helix within a larger protein structure. Suppose that one glutamate residue at some specific position in the helix were mutated to a leucine residue. The mutation could either make the helix more stable, or less stable. i) Describe two situations in which a Glu-to-Leu mutation could make the helix more stable. ii) Describe two situations in which the Glu-to-Leu mutation could make the helix less stable. Explain briefly the basis for the stabilizing and destabilizing effect in all cases.
This problem concerns a "typical" tyrosine residue found on the surface of a globular protein. a) If the pk3 of this residue is 10.1, at what pH will this residue be found in its deprotonated state in 99% of protein molecules? b) How would the presence of a neighboring negatively charged residue effect the equilibrium expression for the dissociation of tyrosine? c) Would the presence of the negatively charged residue raise or lower the pK3 of this tyrosine? Justify and/or explain your answers in 1-2 sentences each for parts b) and c).
Many blood clotting proteins undergo a post-translational modification in which specific glutamic acid residues (Glu) in the protein are converted to gamma-carboxyglutamic acid residues (Gla). See reaction scheme below. An example is the blood clotting protein Factor IX, which has 12 Glu in its N-terminus converted to Gla. This modification gives Factor IX the ability to bind calcium and phospholipid membranes. Bacteria do not have the enzyme required to convert Glu to Gla and therefore Factor IX proteins expressed in bacteria would not have the proper modifications. How might you engineer the translational apparatus of a bacterial cell line so that it produces Factor IX with Gla in the appropriate positions. How would you ensure that only the 12 Glu in Factor IX that are normally converted to Gla and not just all Glu (Limit 5-6 senetnces)?
The charging of a tRNA with an amino acid can be represented by the following equation:amino acid + tRNA + ATP → aminoacyl-tRNA + AMP + PPI where PPI is pyrophosphate (see figure 3–40). in the aminoacyl-tRNA, the amino acid and tRNA are linked with a high-energy covalent bond; a large portion of the energy derived from the hydrolysis of ATP is thus stored in this bond and is available to drive peptide bond formation at the later stages of protein synthesis. the free-energy change of the charging reaction shown in the equation is close to zero and therefore would not be expected to favor attachment of the amino acid to tRNA. Can you suggest a further step that could drive the reaction to completion?