Quiz 3
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Answer following MCQs by selecting one Answer only
1. Which one of the following statements is CORRECT about the mutant form (R132 to H)
of IDH-1 enzyme
A. The mutant IDH-1 uses NADPH as a cofactor of its activity.
B. The mutant IDH-1 converts isocitrate to oncometabolite R-2-Hydroxyglutarate.
C. The mutant IDH-1 converts isocitrate to alpha ketoglutarate.
D. The mutant IDH-1 yields NADPH from NADP+ while producing oncometabolite R-2Hydroxyglutarate.
2. Which one of the following describes enzymatic activity of Ras?
A. ATPase
B. GDPase
C. GTPase
D. ADPase
3. Order the steps involved in membrane insertion and reaction cycle of RAS protein.
a. binding to GDI
b. membrane insertion
c. binding of GAP and GTP hydrolysis
d. nucleotide exchange (GDP to GTP) by SOS
e. binding of effector proteins
f. farnesylation and palmitoylation
A. f, a, b, d, e, c
B. a, d, f, e, c, b
C. f, b, a, d, e, c
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D. d, e, f, a, c, b
4. The switch regions (I and II) of Ras are involved in binding to________.
A. Effector proteins, GDP and GTP
B. Effector proteins
C. GDP and GTP
D. G proteins
5. What one may observe when an oncogenic variant of ras is over-expressed in normal cell by
transfection experiments?
A. Cells may undergo proliferation and form tumors.
B. Cells are likely to demonstrate mutations in other genes like p53.
C. Cells may undergo senescence without any tumorigenic activity.
D. Cells sustain normal growth and proliferation activity.
6. SOS protein is needed to accelerate nucleotide exchange of Ras. Arrange the following
options in correct order pertaining to the nucleotide exchange process.
a. Ras-GDP complex
b. Ras-GTP complex
c. opening of the phosphate binding pocket,
d. SOS binding to Ras,
e. GTP displaces GDP followed by SOS
f. displacement of the phosphate groups, base + sugar portion still bind to Ras,
A. b, d, f, e, a, c
B. d, e, f, a, b, c
C. a, d, c, f, e, b
D. d, e, f, b, a, c
7. Which one of the following statements is “CORRECT”?
A. GTPase activity of Ras is comparable to G proteins.
B. Ras is a very slow enzyme in GTP hydrolysis.
C. GEF is necessary to assist GTP hydrolysis of Ras.
D. Oncogenic Ras proteins hydrolyze GTP more efficiently compared to WT Ras protein.
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8. The oncogenic variant, G12R, of Ras protein is different from the wild type Ras protein,
because_______
A. the G12R binds tightly to GTP but cannot bind to GEF protein.
B. the G12R is unfolded and inactive.
C. the G12R cannot bind either GTP or GDP.
D. the G12R ras binds tightly to GTP but cannot bind to GAP protein.
9. Which one of the following statements is “FALSE?”
A. The structures of inactive Ras (GDP bound) and active form of Ras (GTP bound) are
extremely different.
B. The structures of inactive Ras (GDP bound) and active form of Ras (GTP bound) are found
to vary at the switch regions.
C. In the structure of active Ras, the GTP moiety makes more contact with the amino acids of
Ras whereas in the structure of the inactive Ras, the GDP moiety makes lesser contact with the
amino acids of Ras.
D. The switch regions of GTP bound Ras are more competent for interactions with the effector
proteins for the downstream signaling in comparison to GDP bound Ras.
10. Which one of the following statements correctly explains the inability of GAP for
hydrolysis of GTP of Q61H variant of Ras?
A. The catalytic finger loop Arg residue of GAP cannot be accommodated in the nucleotide
binding pocket of Q61H variant of Ras.
B. GTP binds to Q61H Ras with high affinity compared to wild type Ras.
C. Q61H Ras binds to GAP with low affinity compared to wild type Ras.
D. Q61H Ras is unable to fulfil the catalytic break down of GTP to GDP even in complex with
GAP.
11. Discovery and development of drugs that would target Ras are difficult due to_________.
A. high affinity binding to nucleotides
B. dynamic structures of the switch regions
C. lack of accessible pockets for binding of small molecule drugs
D. all of the above
12. Small molecules showed high promise in the treatment of lung cancer in G12C mutant of
Ras, because ______.
A. these small molecules can irreversibly bind to G12C mutant of Ras
B. these small molecules demonstrated high affinity binding to G12C compared to GTP
C. these small molecules can allosterically change conformations of the nucleotide binding
pocket
D. these small molecules permit efficient binding of GAP
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13. The ‘hydrocarbon staple’ strategy was applied on the SOS derived Ras/SOS interface
peptide demonstrating improved binding to Ras due to_____.
A. stabilization of the hydrophobic interactions within the peptide
B. stabilization of the secondary structure of the peptide
C. stabilization of salt bridge or ionic interactions between the peptide and Ras
D. stabilization of hydrogen bonding interactions between the peptide and Ras
14. Which one of the following statements is “CORRECT” about allosteric inhibitor binding
to Ras.
A. The allosteric inhibitor may bind to the nucleotide binding pocket that essentially competes
out GTP binding.
B. The allosteric inhibitor may bind to the GTP bound state of Ras at the nucleotides binding
pocket forming a ternary complex with Ras-GTP.
C. The allosteric inhibitor may bind to the GTP bound state of Ras and is able to compete out
binding of the effector proteins.
D. The allosteric inhibitors may bind to the GTP bound state of Ras and can stabilize the low
affinity state of effector protein binding to Ras
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