Biochemistry - Post Translational Modification

Question 1

Treatment for anemia that results in a stabilization of HIF-1α protein, so that it is able to stimulate the production of erythropoietin in the kidney.

Answer 1

Oral prolyl hydroxylase inhibitors

Question 1

Ub-activating enzyme, modify Ub so that Ub will react with the lysine on the substrate protein.

Answer 1

E1

Question 3

E3 (Ub-ligases) function in concert with E2 enzymes to confers specificity of the target protein.

Answer 3

Ubiquitin-proteasome ligation

Question 4

E1 donates activated Ub to E2 (Ub-conjugating enzymes) so that E2 can catalyze the attachment of Ub to the substrate protein.

Answer 4

Ubiquitin-proteasome conjugation

Question 5

influences the availability of DNA for transcription.

Answer 5

histone methylation (and demethylation)

Question 6

A transcription factor for many organs that senses oxygen though O2-dependent ubiquitination. When O2 levels normal, it is degraded by the proteasome. In low O2 conditions, proline is not hydroxylated, TF not degraded by E3, and thus translocated to the nucleus where it binds to increase expression of a number of hypoxia-related genes, including erythropoietin (EPO) .

Answer 6

HIF-1a (Hypoxia-Inducible Factor-1a)

Question 6

location of modifying enzymes for O-linked glycosylation

Answer 6

lumen of Golgi

Question 7

The delivery of an elongating polypeptide chain into the lumen of the endoplasmic reticulum (ER)

Answer 7

co-translational insertion.

Question 7

recognizes and binds to the signal sequence of the elongating polypeptide (in cytoplasm)

Answer 7

Signal recognition particle (SRP)

Question 9

amino residues that can be phosphorylated

Answer 9

serine, threonine, or tyrosine (ie seriene to phosphoserine). Presence or absence of a single phosphate group on key regulatory protein has potential to determine if cellwith behave as a cencer cell or not.)

Question 10

binds to SRP; Located within the ER membrane

Answer 10

SRP receptor

Question 10

(heterochromatin) refractory to transcription & recombination

Answer 10

Underacetylated chromatin

Question 10

The advantage of a terminally located signal sequence - aids in the recruitment of translating ribosomes to the surface of the ER

Answer 10

it can be removed by proteases once the protein reaches its final destination.

Question 12

the attachment of a sugar molecule to asparagine (Asn, “N”) residue of a protein to give a rise to a glycoprotein, often involving large and branched glycans. Modifying enzymes reside in ER and Golgi.

Answer 12

N-Linked Glycosylation

Question 13

the addition of a phosphate group to a serine, threonine, or tyrosine residue.

Answer 13

phosphorylation in post-translational modification

Question 14

Catalysts that facilitate assembly without becoming part of the assembled complex. These proteins are the main regulators of protein folding, both during and after translation.

Answer 14

Chaperones

Question 15

a specialized set of amino acids that govern the delivery of polypeptides to specific organelles. can be a continuous stretch of amino acids found at the N- or C-terminus of a protein. removed by proteases once the protein reaches its final destination.

Answer 15

signal sequence

Question 15

carboxylation of glutamate gives glutamate two carboxyl groups (COO-), enabling the sequestration of calcium 2+, bringing these clotting factors close to negatively charged platelet surface.

Answer 15

blood clotting mechanism

Question 16

A pathological condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia) is deprived of an adequate oxygen supply.

Answer 16

Hypoxia

Question 18

Binding of SRP to signal peptide causes a pause in translation. SRP-bound ribosome attaches to SRP receptor in ER membrane. Translation continues and translocation begins. SRP and SRP receptor displaced and recycled.

Answer 18

Mechanism of Co-translational Insertion

Question 18

a well-known mechanism of gene regulation, that involves transfer of one-carbon methyl groups (-CH3) to a substrate and influences the availability of DNA for transcription when done to histone.

Answer 18

Methylation

Question 18

stimulates the production of red blood cells in the bone marrow in response to low blood oxygen Production controlled by controlled by PTM of HIF-1.

Answer 18

erythropoietin (EPO)

Question 18

hydroxyproline residues are not formed, so the proline hydroxylase cannot function adequately. HIF-1a is not recognized by the E3 subunit and HIF-1a is not degraded, and so translated to nucleus to induce expression of EPO.

Answer 18

Under low O2 conditions

Question 19

A barrel-shaped, multi-subunit protein complex that degrades uubiquitin-tagged proteins.

Answer 19

Proteasome

Question 20

Large, branched glycans that exhibit various structures, but all contain mannose and N-acetylglucosamine (GlcNAc).

Answer 20

N-linked oligosaccharides

Question 21

found on mucin proteins (the glycoproteins in mucus secretions) and on proteolgycans of the extracellular matrix.

Answer 21

Extensive O-linked glycosylation

Question 22

presence of hydrophobic residues outside the core of a protein (i.e., within the aqueous environment) is used…

Answer 22

by molecular chaperones to detect that a protein is in an unfolded state

Question 24

(euchromatin) is competent for transcription & recombination

Answer 24

Hyperacetylated chromatin

Question 25

occurs as a co-translational and post-translational modification of proteins, for example, histones, p53, and tubulins. Among these proteins, chromatin proteins and metabolic enzymes are highly represented, indicating that it has a considerable impact on gene expression and metabolism.

Answer 25

acetylation

Question 26

an important part of the cell’s machinery for protein folding, strongly upregulated by heat stress and toxic chemicals, particularly heavy metals such as arsenic, cadmium, copper, mercury, etc

Answer 26

Heat Shock Proteins (HSPs)

Question 27

amino residues that can be N-linked glycosylated

Answer 27

asparagine (Asn, “N”)

Question 28

location of modifying enzymes for N-linked glycosylation

Answer 28

ER and Golgi

Question 29

The covalent addition of N-acetyl galactosamine (GalNAc) to the hydroxyl group of either serine or threonine residues within a protein. In collagens, modification is done to the hydroxyl group of hydroxylysine. Occurs in Golgi, occurs one sugar at a time. Found on mucin proteins and proteoclycans in ECM.

Answer 29

O-Linked Glycosylation

Question 30

cofactors for y-carboxylation reaction

Answer 30

y-glutamyl carboxylase (GGCX) and vitamin K

Question 31

the reversible addition of an acetyl group to a protein or other organic compounds.

Answer 31

Acetylation

Question 32

Controls the expressino of EPO

Answer 32

PTM of HIF-1

Question 34

Multi-step process with E1, E2, and E3 enzymes: activation, conjugation, and ligation.

Answer 34

Ubiquitin-proteasome pathway

Question 34

residues that are covalenetly attached to ubiquitin

Answer 34

lysine

Question 36

Ub is activated when it is attached to E 1(Ub-activating enzyme) in an ATP-dependent fashion. (E1s modify Ub so that Ub will react with the lysine on the substrate protein.)

Answer 36

Ubiquitin-proteasome activation

Question 37

76-amino acid polypeptide that is covalently attached to lysine residues. Can cause alterations in protein function, location and degradation.

Answer 37

Ubiquitination (Ub)

Question 38

catalyze the incorporation of oxygen into organic substrates, including HIF-1, leading to its degradation.

Answer 38

Prolyl hydroxylase

Question 40

It uses the energy of ATP to facilitate protein transfer and to release the folded product. It has the ability to pass the misfolded protein along to the proteasomal machinery for degradation.

Answer 40

Hsp70

Question 41

Ub-conjugating enzymes, can catalyze the attachment of Ub to the substrate protein.

Answer 41

E2

Question 43

Multi-ubiquitin chains bound to a single lysine residue within a protein that undergo rapid proteolysis by proteasome. Used for degradation of mifsolded proteins.

Answer 43

Polyubiquinated proteins

Question 44

amino residues that can be O-linked glycosytaled

Answer 44

serine or threonine

Question 45

An enzyment that forms disulfide bonds between two cysteine residues (S-S) and can also rearrange incorrectly bound S-S bonds to correct the bonding. Located ONLY in the ER. Involved in insulin synthesis.

Answer 45

protein disulfide isomerase

Question 46

Addition of one charged carboxyl group (COO-) to glutamate to generate γ-carboxyglutamate. Performed γ-glutamyl carboxylase (GGCX) with vitamin K as a cofactor. Involved in blood clotting.

Answer 46

y(gamma)-Carboxylation

Question 47

Can be conjugated to a single methyl group or multiple methyl groups to increase the effects of modification.

Answer 47

lysines and arginines

Question 49

Ub-ligases that function in concert with E2 enzymes to confer specificity of the target protein.

Answer 49

E3

Question 50

amino residues that can be y-carboxylated

Answer 50

glutamate. Example, blood clotting proteins

Question 51

small polypeptides (~8 amino acid long) & intact ubiquitin molecules

Answer 51

Degradation products