Suppose that Protein J which is a hypothetical protein kinase receptor was determined tobe related to the progression of cancer through its activation. It was also determined that theprotein exists in the active and inactive forms. The said active form is highly similar to the ProteinK's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized toinhibit Protein J. The affinities of the ligands are shown in the table.Kp valuesActive Protein JInactive Protein JProtein KLigand A10 mM20 nM5 mMLigand B20 nM10 mM15 nMLigand C20 nM15 nM15 nMQuestion:a. Which of the ligands, based on the table, may be expected to be the most potent or havethe highest activity against cancer? Explain.b. Which of the ligands, based on the table, may be expected to be least toxic to normalcells? Explain.

The dissociation constant is the equilibrium constant for the dissociation of a Protein-Ligand…

Answered: Suppose that Protein J which is a…

Biochemistry

9th Edition

ISBN:9781319114671

Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Chapter1: Biochemistry: An Evolving Science

Section: Chapter Questions

Problem 1P

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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: 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.
Some protein kinases are inactive unless they are phosphorylated on key serine or threonine residues. In some cases, active enzymes can be generated by mutating these serine or threonine residues to aspartate. Explain.
Receptor tyrosine kinases such as the epidermal growth factor (EGF) receptor can basically be broken down into three domains: (1) An extracellular, ligand binding domain, (2) A transmembrane domain that must cross through the cell membrane, and (3) an intracellular domain. Match the amino acid with the domain that it would MOST LIKELY be associated with. Lysine (choose (1), (2), or (3) from above) A tyrosine residue capable of being phosphorylated on its hydroxyl group (choose (1), (2), or (3) from above) Isoleucine (choose (1), (2), or (3) from above)
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.
Some protein kinases are inactive unless they are phosphorylated on key serine or threonine residues. In some cases, active enzymes can be generated by mutating these serine or threonine residues to glutamate. Explain. What could you predict about a mutant generated replacing the serine or threonine with alanine.
Which of these is not true about the beta-gamma subunit of the heterotrimeric G protein often coupled to 7TM-receptors? Provide explanations for the answers you choose and do not choose. A. it does not change conformations B. when in heterotrimeric form, it increases affinity of alpha subunit for GDP C. it consists of the GTPase domain and the alpha helical domain D. the subunits are bound together by covalently attached lipid molecules
For the protein Calmodulin-1: 1) this protein have any secondary, tertiary and/or quaternary structures present? 2) Are there any molecular additions to this protein that are not amino acids?For both questions, can you explain if so, where specifically? The protein Calmodulin-1 is stated to have the molecular function of signaling receptor binding which is interrelated with the biological function of calcium-mediated signaling. Can you explain this relationship?
The insulin receptor, on dimerization, cross-phosphorylates the activation loop of the other receptor molecule, leading to activation of the kinase. Propose how this phosphorylation event can take place if the kinase starts in an inactive conformation.
When you think about the primary structure of the mannose-6-P receptor, assuming that it is an integral membrane protein with one membrane-spanning domain and assuming that it has a ERSS, what are all of the different protein domains that must be present in this protein's primary structure to get it to where it needs to go and to carry out all of the functions/activities? (Draw a schematic of the protein structure/sequence and explain each region). What do you think would happen to a soluble protein that normally contains a KDEL tag (ER retrieval) if the tag was cleaved off (where would the protein end up)?
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?
Kinases are enzymes responsible for transferring the terminal phosphate of ATP to the side chains of serines, threonines, and tyrosines in proteins. This is called phosphorylation. Many kinases require autophosphorylation before they can phosphorylate other targets. Discuss how phosphorylation of Ser, Thr, and Tyr changes their chemical properties and how phosphorylation of a kinase might help make it active for other substrates..

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