Protein structure 1

Question 1

What types of hetero groups are there

Answer 1

1. Metals
2. Non-metals (sulphur, selenium)
3. Organic molecules

Question 2

What are the different types of binding of a hetero group

Answer 2

1. Permanent: metals, organic prosthetic groups

2. Transient: substrates, coenzymes, regulators

Question 3

What hetero groups are used in pyruvate dehydrogenase and what are their function

Answer 3

1 Has 5 cofactors:

2. TPP
3. Lipoic acid
4. CoA
5. NAD
6. FAD
7. The cofactors facilitate the oxidative decarboxylation of pyruvate
8. The cofactors have diverse chemical structures

Question 4

What do double bonds mean

Answer 4

1. Double bonds allow very little freedom of rotation

2. The resulting configurations may be either cis or trans

Question 5

What is a chiral centre

Answer 5

1. Chiral centers – asymmetric carbons, exist as two stereo-isomers, which are mirror images (enantiomers)

Question 6

What are dia-steroisomers and how are they labelled

Answer 6

1. dia-stereoisomers - stereoisomers with more than one chiral center; they are not mirror images
2. Absolute configurations: R / S
3. Relative configurations: D / L
4. Nearly all amino acids in proteins possess the L configuration

Question 7

What are amino acids often grouped by

Answer 7

1. Amino acids are commonly grouped by side-chain polarity:
2. Polar side-chains:
3. Due to difference in electronegativity (O,N)
4. Due to difference in electron density (S)
5. Nonpolar side-chains –
6. contain only C-H, C-C, and C-S-C bonds

Question 8

Why is polarity important

Answer 8

1. Underlies non-covalent interactions:
2. Drives protein folding and determines amino acid distribution (protein-protein, protein-water interactions)
3. Drives protein-ligand binding

Question 9

Give some examples of certain chemical derivatives of amino acids

Answer 9

1. Hydroxyproline- post-translational
2. gamma-carboxy-glutamate - post-translational
3. seleno-cysteine- incorporated
4. Pyrrolysine- incorporated

Question 10

What are roles of some amino acid derivatives

Answer 10

1. Some non-protein amino acid derivates are biologically active
2. NMDA
3. Melatonin
4. Serotonin

Question 11

Describe the peptide bond

Answer 11

1. Resonance makes the peptide bond:

2. Partially double –> planar yet not completely rigid

Question 12

How does the primary structure hold biological information

Answer 12

1. Biologically important residues (ligand binding, catalysis) tend to be evolutionary conserved
2. Such residues can be found by aligning sequences of the same protein from different organisms
3. Membrane-bound proteins contain hydrophobic sequences with lengths matching the membrane width

Question 13

How does the protein fold

Answer 13

1. Small protein can fold independently (Anfinsen’s experiment with ribonuclease A)
2. Large proteins fold with the assistance of molecular chaperons

Question 14

What are the two configurations the peptide bond is limited to

Answer 14

1. The rotation of the Cα-N and Cα-C bonds is limited only by steric clashes
2. The ‘allowed’ values of phi and psi angles correspond to two main conformations

Question 15

What are two exceptions to the spiral and extended conformations being highly popular in proteins

Answer 15

1. The two exceptions are Pro and Gly

Question 16

What are different graphic representations of proteins that reveal different properties

Answer 16

1. Wireframe (bonds connectivity)
2. Space-fill (general shape, size) - Space-fill, colored by evolutionary conservation (biologically important regions)
3. Ribbon (topology, secondary structures)
4. Surface (potential binding sites) - Surface, colored by electrostatic potential (complementarity to ligands)
5. Integrated (multiple properties)

Question 17

Describe properties of the right-handed alpha-helix

Answer 17

1. ~30% of residues in globular proteins
2. Radius: 2.3 Å
3. 5-40 residues (10 average)
4. 3.6 residues per turn (5.4 Å)
5. phi = -57o, psi = -47o
6. 1.5 Å rise per residue (compact)

Question 18

Describe Stabilization of right handed alpha helix

Answer 18

1. Mainly nonpolar & vdW interactions

2. Hydrogen bonds – much weaker (exist also in the unfolded state)

Question 19

Describe Amphipathic helices

Answer 19

1. Polar/nonpolar residues face opposite directions
2. Same-type residues appear every 3 or 4 positions
3. Tend to appear on the surface of proteins

Question 20

What are other types of helix

Answer 20

1. The 310 helix
2. The π helix
3. The PPII helix

Question 21

Describe the 310 helix

Answer 21

1. Tighter than α-helix –> unfavorable packing & H-bond pattern
2. Rare (4%), usually found as a single turn at the beginning/end of alpha helices
3. Roles: connecting secondary elements, fixing distortions formed within α-helices (e.g. by Pro)

Question 22

Describe the pi-helix

Answer 22

1. Wider and less tight than α-helix –> sub-optimal vdW interactions, unfavorable H-bond pattern
2. Extremely rare (~0.02% of protein residues)
3. Usually found at the beginning/end of alpha helices
4. Roles: unclear

Question 23

Describe the PPII helix

Answer 23

1. Left-handed, created by proline-rich sequences (but appears also in other sequences)
2. Long and thin -> no backbone H-bonds
3. In structural proteins (e.g. collagen) – creates the tightly packed triple helix
4. In globular proteins – tends to be amphipathic, on surface, functionally important (e.g. bound by SH3 domain)
5. SH3 domain – appears in signaling proteins, recognizes PPII helices in binding partners to relay the signal

Question 24

Describe the beta (extended) conformation

Answer 24

1. ~20% of residues in globular proteins
2. Up to ~10 residues per strand
3. ~3 Å rise per residue (extended)
4. The sheet has a ~30º right twist

Question 25

Why are helices and sheets so common?

Answer 25

1. 90% of polar groups in proteins are hydrogen-bonded

2. Helices and sheets pair polar groups most efficiently

Question 26

What are reverse turns and where do they occur

Answer 26

1. 2nd position - usually cis-Pro (creates a kink )
2. 4th position – Gly (accommodates the kink )
3. 3rd and 4th positions – not conserved (yet, often Asn/Asp)
4. i –> i+3 hydrogen bond

Question 27

What are loops

Answer 27

1. Connect secondary structure elements
2. Usually hydrophilic (polar residues, unsatisfied backbone H-bonds)
3. On the surface
4. Often create binding/active sites of receptors and enzymes
5. Secondary elements are more ordered than loops