biochem exam 2

When considering fibrous proteins, which of the following statements is TRUE? A: Noncovalent interactions contribute to the strength of all of these proteins. B All of them consist of α helix structure. C All of them require vitamin C. D Decrease in amounts of any of them cause scurvy. E All of these are true of fibrous proteins.

A: Noncovalent interactions contribute to the strength of all of these proteins

X-rays Played an Early Role in

Ideas of Protein Structure

Protein Crystals ex

Rubredoxin Azurin

Scurvy

Vitamin C Deficiency Prevents prolylhydroxylase activity

Examine the three sequences below for collagen-like proteins. If hydrogen bonding were the most important feature in determining strength in fibrous proteins, which of the following sequences likely has the highest melting temperature and why? (Note: Flp = fluoroproline; Hyp = hydroxyproline) 1. Pro-Hyp-Gly-Pro-Hyp-Gly-Pro-Hyp-Gly 2. Pro-Flp-Gly-Pro-Flp-Gly-Pro-Flp-Gly 3. Gly-Pro-Thr-Gly-Pro-Thr-Gly-Pro-Thr

"1" because Hyp has OH groups.

• Parallel beta sheets with fewer than 5 strands are rare - Why?

- Parallel beta sheets are probably less stable than antiparallel sheets, all else being equal, - because of the distorted hydrogen bonds they have relative to antiparallel beta sheets

Proteins can denature due to a change in

- pH - temperature - ionic strength

1° Protein Structure

-Lys-Ala-His-Gly-Lys-Lys-Val-Leu-Gly-Ala

The classic experiment demonstrating that reduced and denatured RNase A could refold into the native form demonstrates that _______.

1° structure can determine 3° structure.

The PDB entry 2BEG contains a total of 5 oligopeptides; each oligopeptide participates in ___ unique β sheet/s, where each strand is arranged in a/n ___________ fashion.

2; parallel

The first step in the folding of disordered polypeptides into ordered functional protein is the formation of ______.

2° structure

The α Helix has how many residues per turn

3.6 residues

The PDB entry 1JY4 is a/n ___ strand β sheet, where each strand is arranged in an ___________ fashion.

8; antiparallel

Which of the following series of amino acids is most likely to be buried in the center of a water-soluble globular protein? A Ala, Leu, Phe B Glu, Asp, Lys C Gly, Asn, Ser D Pro, Gln, His

A Ala, Leu, Phe

Which of the characteristics of collagen structure listed below contrubute to the tensile strength of collagen? Please select all that apply. A Collagen is made up of a triplet helix where 3 left-handed helices twist together in a right handed sense. B Collagen includes at repeating sequence of amino acids with glycine every 3 amino acids in a helix with about 3 amino acids per turn. C The three left-handed helices are staggered to allow close packing between glycine residues and rigidity from the bulky and inflexible proline/hydroxyproline.

A Collagen is made up of a triplet helix where 3 left-handed helices twist together in a right handed sense. B Collagen includes at repeating sequence of amino acids with glycine every 3 amino acids in a helix with about 3 amino acids per turn. C The three left-handed helices are staggered to allow close packing between glycine residues and rigidity from the bulky and inflexible proline/hydroxyproline.

Which of the following statements best describes the arrangement of amino acids in the β sheet of 1JY4? A The polarity within each strand mostly alternates at every amino acid, where the charged amino acids mostly point to one side of the sheet, while the aromatic and aliphatic amino acids mostly point to other side of the sheet. B The polarity and arrangement of the amino acids show no general trends. C Each strand of the β sheet has a dramatically different polarity, where the charged amino acids mostly point to one side of the sheet, while the aromatic and aliphatic amino acids mostly point to other side of the sheet. D Each strand of the β sheet has a dramatically different polarity, where the polar strands have amino acids that mostly point to one side of the sheet, while the nonpolar strands have amino acids that mostly point to other side of the sheet.

A The polarity within each strand mostly alternates at every amino acid, where the charged amino acids mostly point to one side of the sheet, while the aromatic and aliphatic amino acids mostly point to other side of the sheet.

Which one of the following statements about the β-sheet is FALSE? A The β-sheet is a type of secondary structure that fulfills the hydrogen bonding requirements of amino acid side chains. B The β-sheet is a type of regular secondary structure. C The β-sheet contains hydrogen bonds between the carbonyl oxygen of one residue and an amide hydrogen of a residue on an adjacent strand. D β-sheets can be parallel or antiparallel. E The side chains in a β-sheet alternate between the two sides of the sheet.

A The β-sheet is a type of secondary structure that fulfills the hydrogen bonding requirements of amino acid side chains.

Azurin

A blue copper protein found in certain* Gram‐negative bacteria that acts as an electron transport protein by a Cu(II)/Cu(I) redox process

Which of the following lines in the figure at right indicates a β hairpin structure?

A, B and D

The Protein Data Bank (PDB) is a database that provides structural information about proteins that may be useful for which of the following? A A researcher studying the changes in protein fold associated with prions. B A researcher classifying structural elements by function. C A researcher designing a compound to bind tightly to a particular region in the protein.

ABC

The Protein Data Bank (PDB) is a database that provides structural information about proteins that may be useful for which of the following? Please select all that apply. A A researcher studying the changes in protein fold associated with prions. B A researcher classifying structural elements by function. C A researcher designing a compound to bind tightly to a particular region in the protein.

ABC

Of the following, which amino acid is most likely to be found in position 1 or 4 on α keratin?

Ala

Which of the following would be most stable based on the information you have learned about protein structure? A A loop region with 8 amino acids. B A β sheet region made up of amino acids Val, Ile, Phe. C An α helix made up of Cys, Pro, and Phe. D A β hairpin with 12 amino acids. E All have equal stability.

B A β sheet region made up of amino acids Val, Ile, Phe.

Which one of the following sequences of five amino acids would most likely be located in the interior of a water soluble globular protein? A Tyr-Phe-Glu-Asn-Leu B Met-Phe-Pro-Ile-Leu C Glu-Asn-Ser-Thr-Gln D Val-Ala-Val-Glu-Val

B Met-Phe-Pro-Ile-Leu

Native protein purifications often require multiple reaction steps in order to purify the protein of interest from other proteins. One method used for protein separation in purification procedures is a change from water to an organic solvent. Which of the following would be accomplished by this solvent change? Please select all that apply. A Proteins with hydrophobic groups on the interior would maintain their native state. B Proteins with hydrophilic groups on the exterior would denature and likely precipitate. C: Proteins with exposed hydrophobic groups would maintain their structure and remain in solution.

B Proteins with hydrophilic groups on the exterior would denature and likely precipitate. C: Proteins with exposed hydrophobic groups would maintain their structure and remain in solution.

When comparing similarities among multiple protein structures, which of the following is false? A Proteins with the same function from a different species are likely to have similar motifs. B Proteins with the same function from different species are likely to be more similar in sequence than in structure. C An effective protein motif is likely be observed in multiple proteins. D Proteins with the same motifs are likely to perform similar functions. E None of the above statements are false.

B Proteins with the same function from different species are likely to be more similar in sequence than in structure.

When comparing similarities among multiple protein structures, which of the following is false? AProteins with the same function from a different species are likely to have similar motifs. B Proteins with the same function from different species are likely to be more similar in sequence than in structure. C An effective protein motif is likely be observed in multiple proteins. D Proteins with the same motifs are likely to perform similar functions. E None of the above statements are false.

B Proteins with the same function from different species are likely to be more similar in sequence than in structure.

Which of the following statements about peptide bonds is FALSE? A The peptide bond exhibits partial double bond character B The peptide bond has restricted rotation around the bond between the carbonyl carbon and Cα. C The peptide bond is planar. D Water is released when a peptide bond is formed.

B The peptide bond has restricted rotation around the bond between the carbonyl carbon and Cα.

Which one of the following statements about peptide bonds is FALSE. Peptide bonds are: A rigid and planar, with partial double-bond character. B charged. C covalent. D involved in forming the primary structure of proteins. E amides.

B charged.

Do alpha helices and/or beta sheets use the full hydrogen bonding capability of the polypeptide backbone.

Both alpha helices and beta sheets use the full hydrogen bonding capability of the polypeptide backbone.

An iron‐containing protein. How was its structure determined?

By a combination of sequencing and spectroscopic methods until the X‐ray crystallography could be done.

Which of the following amino acids combinations have side chains with groups that have the greatest ability to stabilize the tertiary structure of a protein? A Lys and Arg B Cys and Glu C Glu and Lys D Gln and Glu E Pro and Asp

C Glu and Lys

In a ribbon diagram of the structure of 1JY4, each strand of the β sheet is represented by an arrow that points toward the

C-terminus

Protein diseases can be caused by which of the following A mutations affecting the 1° structure. B mutations affecting the 3° structure. C changes in the post-synthetic processing of proteins. D All of the above are potential causes. E None of the above are potential causes.

D

Protein diseases can be caused by which of the following A mutations affecting the 1° structure. B mutations affecting the 3° structure. C changes in the post-synthetic processing of proteins. D All of the above are potential causes. E: None of the above are potential causes.

D

A helix has hydrogen bonds between the carbonyl group from residue "n" and the amino group of residue "n+6," which of the following is TRUE? A It has 3.6 residues per turn. B It is a random coil, not a helix. C It is an α helix. D It has more residues per turn than an α helix. E: It has fewer residues per turn than an α helix.

D It has more residues per turn than an α helix.

Which of the following statements about quaternary structure is TRUE? A Quaternary structure is defined as the 3D structure of proteins with four subunits. B Quaternary structure exists only in proteins containing prosthetic groups. C Quaternary structure requires covalent interactions between polypeptide chains. D Quaternary structure is stabilized by the same types of noncovalent interactions as tertiary structure.

D Quaternary structure is stabilized by the same types of noncovalent interactions as tertiary structure.

Compare the α-helix with the structure of double-stranded DNA. Which statement is TRUE for both structures? A The backbones are on the outside of the helix. B The hydrogen bonds are perpendicular to the axis of the helix. C Hydrogen bonds are the primary determinant of stability. D The helices are right handed.

D The helices are right handed.

Which of the following statements is true regarding collagen? A The inability to hydroxylate proline results in the inability to synthesize collagen. B The α helical structure is ideal for intertwining 3 filaments. C Hydrogen bonds between the ─OH groups of Hyp residues stabilize the helix. D The requirement for glycine every 3rd amino acid is essential for the triplet helix formation. E On average, there is one proline for every hydroxyproline.

D The requirement for glycine every 3rd amino acid is essential for the triplet helix formation

Which of the following has (have) both a favorable hydrogen bonding pattern and φ and ψ values that fall within the allowed Ramachandran conformational regions? A α helix B collagen helix C β sheet D all of the above E none of the above

D all of the above

Which of the following structural proteins has the greatest elasticity? A: α keratin B β keratin C collagen D pleated collagen E A and B are equal

D pleated collagen

The structure of hen egg white protein has been solved and the torsion angles φ and ψ are shown for each residue in the table below. What structure motif most likely forms as a result of this protein sequence? Residue Number φ ψ 31 -61 -44 32 -72 -29 33 -66 -65 34 -67 -23 35 -81 -51 Break Break Break 42 -30 142 43 -142 150 44 -154 121 45 -91 136 46 -110 174 A β Strand connected to another β strand with a break (or loop/turn) in between. B α Helix connect to another α helix with a break (or loop/turn) in between. C β Strand connected to another β strand with a α helix in between. D α Helix connected to a β strand with a break (or loop/turn) in between. E None of the above are correct.

D α Helix connected to a β strand with a break (or loop/turn) in between.

In 1JY4, the presence of _____ at each turn in the β sheet is _________ with the known properties of the amino acid.

D-Pro; consistent

Which of the following changes would not alter the functional characteristics of α keratin? A Increasing the number of residues per turn to 4.1 while maintaining the same amino acid sequence. B Substitution of a hydrophilic amino acid for a hydrophobic amino acid at position a and d of the 7-residue pseudorepeat. C Decreasing the number of cysteine amino acids within each protofilament. D Changing the environment surrounding the protein to one that is more reductive. E All of the above would alter the functional characteristics of keratin.

E All of the above would alter the functional characteristics of keratin.

For type II, residue 3 is usually

Gly

Collagen composition

Gly (1/3)

general formula for collagen

Gly‐X‐Y, where X is often Pro and Y is often hydroxylproline

In a Ramachandran diagram the region representing the angles of φ and ψ that correspond to those commonly made by an amino acid that favors a left-handed α helix are different from those angles commonly made by an amino acid that favors right-handed α helix formation. Which of the following statements provides a plausible explanation for this difference?

Groups which would normally undergo high steric hindrance in the right-handed arrangement are separated maximally in the left-handed arrangement.

Hard keratins vs soft keratins

Hard keratins (hair, nail, horn) have many disulfide crosslinks relative to soft keratins (skin).

H bonding in alpha helix vs Beta sheets

H‐bonding is within a chain for an alphahelix • H‐bonding is between chains for beta sheets

You have been shown the detailed 3-D structure of an unknown protein. The information indicates that the protein's non-polar amino acid side chains are all exposed on the surface, whereas its polar side chains are all "buried" in the interior. What can you conclude about this protein?

It is likely to be an integral membrane protein.

Myoglobin was the first protein X-ray structure to be completed by who

John Kendrew, 1958

first protein X-ray structure to be completed

Myoglobin

Protein dynamics is a field of study that examines the movements with in a protein. Which type of protein structure determination would be most useful to study this type of change?

Nuclear Magnetic Resonance (NMR)

When solving a protein structure using X-ray crystallography, the crystallographer generates a 3-D grid called an electron density map based on the observed diffraction pattern. The higher the resolution, the more detailed the electron density map and therefore the easier it is to identify what atoms (and therefore what amino acids) are in a given position. Based on the three choices below, in which of the following groups could the two of amino acids be the easiest to differentiate regardless of resolution? I. Leucine vs. Isoleucine II. Phenylalanine vs. Alanine III. Glutamate vs. Glutamic acid

Only those in group II could be differentiated.

For types I and II residue 2 is often

Pro

Conventional one dimensional NMR spectroscopy is not generally an effective tool for determination of protein structure because...

Proteins (including small proteins) have a high number of hydrogen atoms. and The NMR spectra exhibit high peak overlap.

Which of the following amino acid residues form hydrogen bonds with Ala residues located in an α-helix?

Residues located within the same α-helix.

Which of the following describes the entire three-dimensional structure of a single polypeptide?

Tertiary structure

What is the primary driving force in the formation of protein tertiary structure?

The exclusion of non-polar substances from aqueous solution.

Irregular loops of secondary structure tend to be located on the outside of folded proteins because:

The peptide bonds in loop structures are free to form H bonds with water.

alpha keratin vs alpha helices

There are 3.5 residues per turn in keratin versus 3.6 as with α helices

Why do Tyr and/or Trp residues tend to destabilize an α-helix when they occur next to each other in a protein?

There is steric hindrance between the bulky Tyr and/or Trp side chains.

What is the major role played by prosthetic groups in proteins?

They provide reactive groups not found in amino acid side chains.

Peptide Bonds Assume what Conformation

Trans

Collagen helix

Triple Helix

exception of Peptide Bonds Assume trans Conformation

X-Pro bonds

A domain is:

a folded segment of polypeptide with a separate hydrophobic core.

Connecting Adjacent β Strands:

antiparallel strands only need small loops but parallel strands need more complex loops

Regular secondary structures are often joined by stretches of peptides called reverse turns or β _______

bends

- Antiparallel

beta sheets (N to C vectors)

Parallel

beta sheets N to C vectors

Helix- _____is the phenomenon in which side chains of residues just outside α-helices make hydrogen bonds to the backbone groups of the four terminal residues of the helix.

capping

Gly to Ala mutation in the structure of collagen causes

causes distortion of the helix.

In most peptide groups the ______ conformation is not sterically favored

cis

In 2BEG, the amino acids within each strand of the β sheets _________ sequentially and significantly alternate between polar and nonpolar.

do not

keratin & collagen both have

elongated shapes dominated by a single type of secondary structure

Beta Sheets can contain how many polypeptide strands?

from 2 to about 22 polypeptide strands, with 6 being the average

The α Helix setup

helix is set up to be compact and allow H‐bonding between carbonyl oxygens of residue n and amide NH groups of residue n + 4.

WP: Protein structures can be predicted by using the technique __________ modeling, in which sequences are aligned with those of structurally characterized proteins.

homology

keratin & collagen serve as examples of

important structural elements

The crystal structure of D.g. Rd has been determined by

means of both an Fe single‐wavelength anomalous dispersion (SAD) signal and the direct method, and refined to an ultra‐high 0.68 Å resolution, using X‐ rays from a synchrotron

A Coiled Coil is where

nonpolar residues a & d interact with a' and d' in keratin, where each coil has an approx. abcdefg motif

The low pH found in the gut can enhance the digestibility of dietary protein by causing ___.

protein denaturation

Chaperonins such as the GroEL/ES system

require ATP hydrolysis.

In the absence of ascorbic acid, prolyl oxidase is unable to oxidize proline residues in collagen to hydroxyproline, resulting in:

scurvy

Ramachandran Diagram

shows common ψ/ϕ combinations

1934 J. D. Bernal and Dorothy Crowfoot Hodgkin show

that crystals of pepsin give a discrete diffraction pattern when placed in an X-ray beam

1934 J. D. Bernal and Dorothy Crowfoot Hodgkin's discovery supported what?

the idea that proteins had ordered structures, not random structures

Greek letter Phi (ϕ) measures

the torsion angle around the α-carbon to amide N bond. 180 degrees here.

Greek letter Psi (ψ) measures

the torsion angle from the αcarbon-to-α carboxylic acid carbon bond. 180 degrees here.

Based on what you know about fibrous protein structure and sequence, what type of fibrous protein is this sequence most likely to from (You can assume that the protein is longer than what is shown and is repeating as shown, also note the polarity of each amino acid.)? Val - Cys - Lys - Val - Cys - Ala - Cys - Val - Cys - Lys - Val - Cys - Ala - Cys

α Keratin.

The Pro residues in collagen prevent

α helix formation (they lack a backbone N‐H, among other reasons).

In a Ramachandran diagram, a larger area represents sterically allowed torsion angles of φ and ψ that are allowed in _____ rather than in ______ because there is greater opportunity for separation of amino acid side chains.

β sheet...α helix

Reverse Turns in Polypeptide Chains link what

β-strands with small loops, usually at the exterior surface

Dorothy Hodgkin (12 May 1910 - 29 July 1994) solved structures of:

•Penicillin (1949) •Vitamin B12(1954) •Insulin (1969)