MCB Exam 2 Sapling/Discussion Questions

What is the indication for each of the violations of Lipinski's rules?

-over 500 MW, too big -more than 10 H bond acceptors, more than 5 H bond donors-- too polar -more than log P of 5, too hydrophobic, cannot leave membrane once it goes through

How many phosphoester bonds/phosphoanhydride bonds in: AMP ATP

1, 0 1, 2

Tightly packaged cellular DNA is supercoiled and most DNA is negatively supercoiled. Identify the true statements about negative supercoiling in DNA: 1. Negative supercoiling helps in strand separation during replication and transcription 2. Supercoiling permits the compacting of DNA 3. Negative supercoiling occurs as a result of the underwinding of circular or protein-bound DNA 4. Negatively supercoiled DNA has fewer base pairs per turn than relaxed DNA 5. Negative and positive supercoiling give rise to mirror image helices with similar functional characteristics

1. Negative supercoiling helps in strand separation during replication and transcription 2. Supercoiling permits the compacting of DNA 3. Negative supercoiling occurs as a result of the underwinding of circular or protein-bound DNA

How many H bonds between this DNA strand and its complementary DNA: 5'-GGAGTGA-3'

18 (3 for GC, 2 for AT)

average wavelength at which DNA absorbs UV light

260 nm

What is the Lk for negatively supercoiled 3045 bp if it is underwound by 4 complete turns?

286

What is the Lk for a relaxed, closed-circular DNA with 3045 base pairs?

290 (3045 base pairs/10.5 base pairs in one turn)

What is the complementary sequence? 5'-TGACGTGAT-3'

3'-ACTGCACTA-5'

The sequence for this short segment of nucleic acids is (from 5' to 3')

5'-GAT-3'

What is the amount of noncoding DNA in the human genome?

98%

-favored form of dehydrated DNA -26 A helix diameter -right handed

A form

Which of the following correctly explains why histones are so useful in packing DNA? A) Histones contain large numbers of basic residues. B) Histones have very large sizes. C) Histones are heavily negatively-charged. D) Histones are very hydrophobic.

A) Histones contain large numbers of basic residues.

Which ligand binds the tightest? A) Kd = 10^-9 B) Kd = 10 ^ -03 C) 30% occupancy at 1 micrometer D) 80% occupancy at 10 nanometers

A) Kd = 10^-9 (smaller kd, tighter binding)

The two strands of DNA double helix can be separated by heating. If you raised the temperature of a solution containing the following three DNA molecules, which one would be the most difficult to melt? A. 5'-GCGGGCCAGCCCGAGTGGGTAGCCCAGG-3' 3'-CGCCCGGTCGGGCTCACCCATCGGGTCC-5' B. 5'-ATTATAAAATATTTAATACTATATTTAAA-3' 3'-TAATATTTTATAAATTATGATATAAATTT-5' C. 5'-AGAGCTAGATCGAT-3' 3'-TCTCGATCTAGCTA-5' D. There would be no difference.

A. (It's long, has a high G-C concentration)

Gene is one of the key terms in biology. Which of the following statements about gene is correct? A) Gene usually means a segment of DNA that contains the instructions for making a particular protein. B) All genes code for proteins. C) The complete sequence information of all the genes present in an organism is collectively called genome. D) All of the above.

A. Gene usually means a segment of DNA that contains the instructions for making a particular protein

If there is an AT-rich strand and a GC-right strand and they are both exposed to heat and denatured, which will be the top strand (denatured faster)?

AT-rich

Based on statistics for the human genome, the mean gene size is about 27,000 nucleotide pairs. Consider the fact that a typical human protein is composed of about 500 amino acids, which of the following statements is most reasonable? A) Each human gene contains enough information to simultaneously code for a few copies of the same protein. B) Only a very small portion of a typical human gene carries coding sequences. C) Distinct from many other species in which each amino acid is specified by 3 nucleotides, each amino acid in a human protein is specified by 50 nucleotides. D) Most human genes do not have introns.

B) Only a very small portion of a typical human gene carries coding sequences.

Which of the following is true about the replication origin? A) Replication origin is only found in linear chromosomes, thus bacterial DNA replication does not rely on replication origin. B) Replication origin often contains an AT-rich region. C) The first protein that binds to replication origin to initiate DNA synthesis is helicase, because melting double strand DNA to generate single-stranded templates occurs the earliest in DNA replication. D) Telomere is a part of replication origin.

B) Replication origin often contains an AT-rich region. (opens easily)

Glutathione is an important tri-peptide that plays an important role in drug metabolism. Which of the following is true regarding glutathione? A. Glutathione is a type of oxidase that can add a hydroxyl group to the drugs found in our body. B. Glutathione can be conjugated to certain drugs to facilitate their excretion. C. Glutathione is a competitive inhibitor for phosphodiesterase 5. D. Glutathione acts as a carrier peptide in our blood stream to facilitate the distribution of the drugs to the desired cellular compartment.

B. Glutathione can be conjugated to certain drugs to facilitate their excretion.

Which of the following will most likely lead to an enrichment of PHD- or chromodomain-containing proteins in a chromatin region? A) Acetylation of histone tails  B) Methylation of histone tails  C) Ubiquitination of histone tails  D) Phosphorylation of histone tails.

B. Methylation of histone tails

White gene controls the eye color in fruit-fly. A rare chromosome inversion event brings the White gene from its normal locus to a region that is very close to heterochromatin. As a consequence, the mutant fruit-fly has a different eye color. Which of the following is a true statement regarding this phenomenon? A) This is an example that DNA replication is less accurate in the regions that close to heterochromatin. B) This is an example of position effect on gene expression. C) Expression of White gene is enhanced in the mutant fruit-fly, and that is why its eye color is a patch of red and white. D) This phenomenon is caused by X-inactivation in fruit-fly.

B. This is an example of position effect on gene expression

The size of our genome is enormously large. In a typical human cell with 23 pairs of chromosomes, the total length of DNA is about 6.4 billion nucleotide-pairs. How many nucleosomes are present in a typical human cell? Note one billion is a thousand million. A) About 10 millions.  B) About 21 millions. C) About 32 millions.  D) About 1 billion.

C. About 32 millions (each nucleosome has about 200 base pairs, so 6.4 billion/200)

Which of the following is a type of epigenetic inheritance? A) A substitution of A to C on the coding strand of a gene, and the change passes on to the progeny cells. B) Inheritance of organelles such as mitochondria from the parent cell. C) Chromatin change silences a gene, and the gene remains silent in the progeny cells due to the inheritance of the chromatin structure. D) A replacement of a DNA segment of a gene, and the change passes on to the progeny cells.

C. Chromatin damage silences a gene, and the gene remains silent in the progeny cells due to the inheritance of the chromatin structure.

A drug candidate that binds to its target with a very low value of kD means A. This drug candidate has very low affinity to the target. B. This drug candidate has very good ADME property. C. It takes very low concentration of the drug candidate to bind sufficient amount of the target. D. This drug has a low tendency to dissolve in the membranes.

C. It takes a very low concentration of the drug candidate to bind sufficient amount of the target.

We learned first quarter that western blotting is a powerful method that allows the detection of a protein of interest, but this method requires that we have prior knowledge about the protein to be detected. Which of the following methods allows us to gain the identity of an unknown protein, such as an interesting band on the SDS-PAGE gel? A. PCR B. FRET C. Mass spectrometry D. X-ray crystallography

C. Mass spectrometry

To examine whether proteins A and B interact, you have fused protein A to blue fluorescent protein (BFP, excited by violet light and emits blue light) and protein B to green fluorescent protein (GFP, excited by blue light and emits green light) and expressed both fusion proteins in the same cells. Interaction between proteins A and B is considered to occur if A) the cells emit green light when they are excited with blue light. B) the cells emit blue light when they are excited with violet light. C) the cells emit green light when they are excited with violet light. D) the cells emit violet light when they are excited with blue light.

C. the cells emit green light when excited by violet light

The enzymes that are responsible for oxidizing foreign compounds in the liver to assist in their excretion are what?

Cytochrome P450

The famous "Photo 51," i.e., the first high quality X-ray image of crystallized DNA fiber, was generated by: A) James Watson  B) Francis Crick C) Frank Holliday  D) Rosalind Franklin

D. Rosalind Franklin

What causes the formation of 30-nm chromatin fiber from "beads on a string" type of chromatin? A) The action of histone H1. B) The interactions between the tails of histone core and the DNA from adjacent nucleosomes. C) Removal of acetyl groups from the histone tails. D) All of the above.

D. all of the above

-stable to alkaline hydrolysis -contains equal amounts of purines and pyrimidines -contains the pyrimidine thymine

DNA

Nucleic acid without OH on the 2' C

DNA

DNA structure is describes as beads on a string, and the string is

DNA molecule

What is the definition of noncoding DNA?

DNA sequences that do not encode proteins

Which of the following types of molecules are important drug targets? A. DNA B. RNA C. Receptors D. Enzymes E. Both C & D

E. both C and D (enzymes and receptors)

What are the linking numer (Lk), twist number (Tw) and the writhing number (Wr) of the molecule shown on the left?

Lk: 4, Tw: 4, Wr: 0

-sometimes containing the unusual nucleoside pseudouridine -can be hydrolyzed in alkaline solution -contains the sugar ribose

RNA

If organism X has 21.3% A, predict the rest of the compositions If organism Y has 31.3% A, predict the rest of the compositions Which will have a higher melting DNA?

T= 21.3%, G=C=28.7% T= 31.3%, G=C=18.7% X will have higher because more G-C

-left-handed -18 A helix diameter -anti purine conformation possible

Z form

Where does the N-glcosidic bond form?

between N of base and 1C of monosaccharide

2 OH on sugar, no phosphate, cytosine

cytidine

Select phrases that accurately describe the most common DNA double helix 1. helical turn consists of about 3.4 nucleotides 2. base pairs have a spacing of 3.4 A 3. nitrogenous bases are exposed to the solvent, whereas the sugar-phosphate backbone of each nucleotide strand is on the interior of the double helix 4. phosphodiester bonds between nucleotide residues run in opposite directions in the two strands 5. DNA contains equal amounts of AT and GC

2. base pairs have a spacing of 3.4 A 4. phosphodiester bonds between nucleotide residues run in opposite directions in the two strands 5. DNA contains equal amounts of AT and GC

Shown here is a base-pair between G and C found in DNA double helix. Identify the circled group that is a hydrogen-bond donor and is located in the major groove of the DNA helix.

B (REVIEW)

-most stable form under physiological conditions -20 A helix diameter -major groove is wide and deep -right-handed

B form

-right-handed -10 bp per turn -3.4 A rise per base pair -19 A helical diameter -deep and wide major groove -narrow and shallow minor groove

B form DNA

HAT can add acetyl groups to lysine residues on histone tails. Which of the following statements is true regarding the action of HAT and acetylation of lysine residues on histone tails? A) Acetylation of histone tails by HAT preserves the positive charge on histone tails. B) Acetylation of histone tails by HAT diminishes the affinity of histone tails to DNA. C) Acetylation of histone tails always leads to gene silencing. D) Acetylation is highly prevalent in the telomere region of chromosome.

B) Acetylation of histone tails by HAT diminishes the affinity of histone tails to DNA.

Which of the following describes the correct sequence of events in the assembly of histone octamer? A) H2A forms a dimer with H3; H2B forms a dimer with H4, and then two H2A/H3 dimers combine with two H2A/H4 dimers to form an octamer. B) H2A dimerizes with H2B; H3 dimerizes with H4; two H3/H4 dimers form a tetramer, which binds two H2A/H2B dimers to form an octamer. C) H2A dimerizes with H4; two H2A/H4 dimers attract two copies of H2B and H3 to form an octamer. D) H2A dimerizes with H2B; H3 dimerizes with H4; two H2A/H2B dimers form a tetramer, which attracts two H3/H4 dimers to form an octamer.

B) H2A dimerizes with H2B; H3 dimerizes with H4; two H3/H4 dimers form a tetramer, which binds two H2A/H2B dimers to form an octamer.

Many proteins such as transcription regulators can recognize specific DNA sequences without prying open the double helix structure by these proteins. Which of the following provides a reasonable explanation for why this is the case? A) These proteins typically form a complex with helicase, which can pry open the double helix. B) These proteins form unique interactions with DNA in the major groove where each base-pair can be clearly distinguished. C) These proteins form complex with code-reader proteins, which can read DNA sequence. D) These proteins form unique interactions with DNA in the minor groove where each base-pair can be clearly distinguished.

B) These proteins form unique interactions with DNA in the major groove where each base-pair can be clearly distinguished. (more variation present, easy to recognize on the major groove side, whereas there is ambiguity associated with the minor groove side)

H1 is one of the important factors in determining the chromatin structure and gene expression. Considering a chromatin region with a very high content of H1, which is true? A) Genes packaged in this region are actively transcribed. B) This region should be densely packaged, which should not be compatible with gene expression. C) This region should have relatively less amount of nucleosomes. D) This region most likely contains a replication origin.

B) This region should be densely packaged, which should not be compatible with gene expression. (H1 also called linker)

In female mammals, one X-chromosome is completely inactivated and the entire chromosome is composed of heterochromatin. Which of the following is true regardign X-inactivation in mammals? A) X-inactivation occurs at a stage after the birth. B) X-inactivation requires active expression of a gene at the locus of XIC on X-chromosome. C) XIST is a protein expressed from X-chromosome that is essential for X-chromosome inactivation. D) As cells divide, the progeny cells always randomly select one X-chromosome to inactivate.

B) X-inactivation requires active expression of a gene at the locus of XIC on X-chromosome. (XIST is not a protein expressed from X-chromosome, but it is a long RNA that binds to the X chromosome and recruits the protein that will end up compacting the chromosome)

Histone proteins: A) release bound DNA to enable nuclear division during mitosis B) associate with DNA and compact DNA within the nucleus C) enable mitochondria DNA to replicate with nuclear DNA before mitosis D) organize DNA into separate chromosomes at the beginning of mitosis

B) associate with DNA and compact DNA within the nucleus

What is the complementary sequence for the DNA strand with a sequence of 5'-ATG GAC TTC AGC CT-3'? A. 5'-TAC CTG AAG TCG CA-3'  B. 5'-AGG CTG AAG TCC AT-3' C. 5'-UAC CUG AAG UCG CA-3'  D. 5'-AGG CUG AAG UCC AU-3'

B. 5'-AGG CTG AAG TCC AT-3'

Which of the following types of inhibitor can inhibit an enzyme independent of substrate concentration? A. Competitive inhibitor B. Non-competitive inhibitor C. Uncompetitive inhibitor D. All of the above

B. Non-competitive inhibitor

Overdose of acetaminophen (i.e. Tylenol) can lead to liver failure. This is because: A. Acetaminophen is toxic and it can kill liver cells B. Overdose of acetaminophen leads to depletion of glutathione, which causes accumulation of the toxic metabolic by-product from acetaminophen C. We need pain in the liver to keep it healthy D. All of the above

B. Overdose of acetaminophen leads to depletion of glutahione, which causes accumulation of the toxic metabolic by-product from acetaminophen

Ubiquitination is an important type of post-translational modifications that typically occur on a lysine residue. Which of the following correctly describes the chemical linkage between ubiquitin and the protein being modified? A) The linkage is non-covalent because ubiquitin is a small protein. B) The linkage is an amide bond, which is also called isopeptide bond. C) The linkage is ionic, specifically, the positive charge of a lysine residue form ionic interaction the negatively charged carboxyl terminal of ubiquitin. D) The linkage is a disulfide bond.

B. The linkage is an amide bond, which is also called isopeptide bond.

Considering the molecule shown on the right, which of the following statements is correct? (ribose, no phosphate group, purine with one keto and one amino group) A. This molecule is a type of deoxyribonucleotide and can be used by DNA polymerase for DNA synthesis. B. This molecule is a nucleoside, and its name is guanosine. C. This molecule is a nucleoside, and its name is guanine. D. This molecule is cytidine, which can be phosphorylated to become a nucleotide.

B. This molecule is a nucleoside, and its name is guanosine (guanosine because it is a purine with two groups extending off it, not attached to a phosphate so it is a nucleoside, not deoxy)

Methylation of lysine or arginine residues in histones is catalyzed by: A) Histone deacetylase  B) Histone acetyl-transferase C) Histone methyltransferases D) Histone demethylase

C) Histone methyltransferases

PCNA, i.e., proliferating cell nuclear antigen, is a sliding clamp that works together with DNA polymerase during DNA synthesis. Considering the structure of DNA, all the intermolecular forces that mediate DNA and protein interaction, and how sliding clamp works, what amino acid residues on the alpha helices of PCNA that surround the double helix of DNA would you suspect are most important for the function of PCNA? A) Residues with smaller, non-polar side chains (e.g. G, A, & V) B) Residues with larger, non-polar (hydrophobic) side chains (e.g. F & W) C) Residues with basic side chains (K & R) D) Residues with acidic side chains (D & E)

C) Residues with basic side chains

Which of the following factors contributes to packing nucleosomes into highly condensed structures? A) low concentration of H1 B) heavy acetylation of histone tails C) heavy methylation of histone tails D) heavy phosphorylation of histone tails

C) heavy methylation of histone tails

The drug named indinavir is very effective in treating: A. Malaria B. Sickle cell anemia C. AIDS D. Inflammation

C. AIDS

Recruitment of (or attracting) HMT, i.e., enzymes that catalyze histone methylation, to a chromatin region can potentially lead to: A) binding of PHD domain-containing proteins to that chromatin region. B) tighter packing of that chromatin region. C) silencing of the genes packaged in that chromatin region. D) All of the above.

D) All of the above.

In which of the following post-translational modifications, the modifier is not a simple chemical group but rather a small protein? A) Methylation B) Phosphorylation  C) Acetylation  D) Ubiquitylation E) All post-translational modifications use a simple chemical group as the modifier.

D) Ubiquitylation

Histone proteins play fundamental roles in all eukaryotes. One important principle in biochemistry is structure determines function. What structural features of histone proteins makes them suitable for their important roles in biology? A) Histone proteins are fibrous proteins so they can wrap around DNA double helix. B) Histone proteins contain large proportions of basic residues on their surface so they can form favorable interactions with DNA. C) Core histones have highly flexible tails that extend out from the nucleosome core particle, which allows extensive chemical modifications, thereby providing a means for regulating gene expression. D) Both B and C.

D. Both B and C

ADME property of a drug candidate refers to its extents and rates of what?

absorption, distribution, metabolism, excretion

-antiparallel strands of DNA -capable of anti form of pyrimidine attachment

all DNA

Where does phosphate ester bond form?

between P of phosphate and O connected to the 5'C on sugar

-sugars are connected with a 3'-5' phosphodiester link -contains the purine adenine

both RNA and DNA

-state of DNA orgnization

both heterochromatin and euchromatin

-found in RNA and DNA -contain a base and a monosaccharide -may contain either ribose or deoxyribose

both nucleotide and nucleoside

Treatment by the drug sildenafil (brand name "viagra") can lead to an increase in the level of this signaling molecule ________, and sildenafil is this type of inhibitor _______ for phosphodiesterase 5.

cGMP, competitive

order from greatest to smallest tight helical fiber supervoil nnucleosome DNA double helix histone protein chromosome

chromosome supervoil tight helical fiber nucleosome histone protein DNA double helix

2 OH on sugar, not connected to phosphate, cytosine base

cytidine

1 OH on sugar, 1 phosphate, adenosine

deoxyadenosine monophosphate

one OH on sugar, connected to phosphate, adenosine base

deoxyadenosine monophosphate

one OH on sugar, not connected to phosphate, cytosine base

deoxycytidine

1 OH on sugar, no phosphate, thymine

deoxythymidine

-loosely packed -high level of transcription -found in prokaryotes -major state of most genes

euchromatin

-the looser form of chromatin -the form chromatin takes most often during transcription

euchromatin

How do we calculate kD?

find the concentration of the free ligand at the point where half the active sites have been saturated

-nucleotide sequence that can encode a protein -humans have about 21,000 -thousands of base pairs long

gene

-collection of genetic information in an organism -defines human as a species -millions of base pairs long

genome

-the denser form of chromatin -the form chromatin takes most often when transcription is not occurring

heterochromatin

-tightly packed -low level of transcription -major state of the inactive X chromosome

heterochromatin

The more darkly-staining form of chromatin

heterochromatin

A core composed of eight ____ proteins interacts with DNA through hydrogen bonding and ioninc bonds

histone

Aspirin is one of the most commonly used drugs, and it functions primarily via inhibiting prostaglandin H2 synthase. What type of inhibitor is aspirin?

irreversible (acetyl binds irreversibly to serine and inhibits prostaglandin H2 synthase)

How does an epigenetic change differ from a mutation?

mutation alters the nucleotide sequence in DNA, an epigenetic change does not alter the DNA sequence, but can be inherited by daughter cells (i.e. chromatin conformation of DNA)

-in base composition, %T=%G -bases are attached to sugars in an alpha N-glycosidic linkage -contains the sugar 3'-deoxyribose

neither DNA or RNA

-do not contain phosphate group -product when a base bonds to C1 of the ribose or deoxyribose

nucleoside

______ is a DNA-protein complex

nucleosome

specialized proteins associate with DNA in the nuclease, forming DNA-protein complexes. What is the term for a segment of DNA wrapped around a core of eight proteins?

nucleosome

DNA structure is describes as beads on a string, and the beads are ____

nucleosomes

-contains a base, monosaccharide, and a phosphate group -monomers of nucleic acid -can be named as deoxyguanosine-5'-monophosphate

nucleotide

The linkage that connects two sugars together and employs the phosphate is called

phosphodiester linkage (between 5' C of ribose and 3' C of ribose)

How can you find the Tm?

point at which half the helicase structure has been lost

-contains two heterocyclic rings -contains four rign nitrogens -guanine

purines

What does cytosine look like?

pyrimidine (1 ring), 2 N in structure, 1 keto group, 1 amino group

What does thymine look like?

pyrimidine (1 ring), 2 N in structure, 2 keto groups, methylated (basically methylated uracil)

-contains one heterocyclic ring -contains only two ring nitrogens -cytosine -uracil

pyrimidines

The linear chromosomes of eukaryotes are not mistaken by the cells as broken DNA molecules in need of repair, because they contain unique sequence elements called:

telomere

How does Lk change when there is a break in one strand?

undefined (has to be a circular strand to have Lk)