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- Between direct and indirect allosteric kinase inhibitors, which do you think requires a larger conformational change in response to binding of the allosteric modulator? Why?Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: a. Which of the ligands, based on the table, has the highest specificity in binding to the target Protein J?Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: a. Which of the ligands, based on the table, may be expected to be the most potent or have the highest activity against cancer? Explain. b. Which of the ligands, based on the table, may be expected to be least toxic to normal cells? Explain.
- Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: Describe the relative binding affinities of Ligand A to Protein K and to the active and inactive forms of Protein J. Determine which will Ligand A bind with the highest, medium, and lowest affinity.GTP binding proteins are molecular switches. How do GTP binding proteins work? Provide two examples of GTP binding proteins that function in intracellular protein transport. Make a drawing that illustrates the function of each of these proteins in their respective roles. Predict the direct outcome of a mutation that: Inhibits GTPase activity Inhibits interaction with the GEFIdentify eight general types of protein kinases found in eukaryotic cells, and explain what factor is directly responsible for activating each type.
- CAMP (cyclic adenosine monophosphate) is a molecule that can activate kinase enzymes allosterically in the cytoplasm. Describe the effects of CAMP molecules on kinase enzymes.15.3 Explain the fellovine diaeram: prospective nuclear protein nuclear Ran HYDROLYZES ITS BOUND GTP, localization Ran-GDP ignal Ran-GDP DISSOCIATES PROTEIN BINDS FROM RECEPTOR TO RECEPTOR nuclear pore CYTOSOL NUCLEUS Ran-GTP BINDS PROTEIN DELIVERED TO NUCLEUS TO RECEPTOR Ran-GTP 15.4 EXplain the followine.diBEram: SRP displaced and released for reuse MRNA ribosome signal- recognition particle (SRP) CYTOSOL growing- polypeptide chain ER signal sequence ER LUMEN SRP receptor protein translocator Ngam 1514 Iereoog ed.arinde 15.5 Explain the following.diaeram: newly synthesized soluble proteins for constitutive newly synthesized plasma membrane lipids transport vesicde secretion CONSTITUTIVE SECRETION unregulated exocytosis plasma membrane newly synthesized plasma membrane protein extracellular signal such as trans Golgi network homone or neurotransmitter signal transduction REGULATED SECRETION regulated екосуtosis secretory vesicle storing secretory proteins Golgi apparatus CYTOSOL…Signal-transducing heterotrimeric G proteins consist of three subunits designated α, β, and γ. The Gα subunit is a GTPase switch protein that cycles between active and inactive states depending on whether it is bound to GTP or to GDP. Review the steps for ligand-induced activation of effector proteins mediated by the heterotrimeric G proteins. Suppose that you have isolated a mutant Gα subunit that has an increased GTPase activity. What effect would this mutation have on the G protein and the effector protein?
- Protein Kinase A can phosphorylate different proteins in different cells. Explain the role of AKAP’s (A Kinase Anchoring Protein’s) in determining which substrates of Protein Kinase A will get phosphorylated in particular cells.Figure 9.8 HER2 is a receptor tyrosine kinase. In 30 percent of human breast cancers, HER2 is permanently activated, resulting in unregulated cell division. Lapatinib, a drug used to treat breast cancer, inhibits HER2 receptor tyrosine kinase autophosphorylation (the process by which the receptor adds phosphates onto itself), thus reducing tumor growth by 50 percent. Besides autophosphorylation, which of the following steps would be inhibited by Lapatinib? Signaling molecule binding, dimerization, and the downstream cellular response. Dimerization, and the downstream cellular response. The downstream cellular response. Phosphatase activity, dimerization, and the downsteam cellular response.Suppose that in the formation of phenylalanine hydroxylase mRNA, the exons of the pre-mRNA fail to splice together properly and the resulting enzyme is nonfunctional. This produces an accumulation of high levels of phenylalanine and other compounds, which causes neurological damage. What phenotype would be produced in the affected individual?