1. Principles of biomolecular structures Flashcards
Define primary, secondary, tertiary, and quaternary structures
Primary: The sequence of amino acids Secondary: backbone conformation (a helices/b sheets) Tertiary: 3D conformation “fold” of secondary elements Quaternary: association of multiple tertiary structures
What is the most common sereoisomer of an amino acid?
The L-stereoisomer
Name the 5 + 1 aliphatic amino acids (1 letter, 3 letter, full name)
Glycine, (Gly, G) H Alanine (Ala, A) CH3 Proline (Pro, P) Loop Valine (Val, V) V Leucine (Leu, L) Y Isoleucine (Ile, I) L
Name the 3 + 1 hydrophobic amino acids (1 letter, 3 letter, full name)
Methionine (Met, M) CH3-S-CH2-CH2 Tryptophan (Trp, W) B Phenylalanine (Phe, F) phe-CH2 Isoleucine (Ile, I) L
Name the 6 Polar amino acids (1 letter, 3 letter, full name)
Serine (Ser, S) OH-CH2 Threonine (Thr, T) V-OH Tyrosine (Tyr, Y) OH-phe Asparagine (Asn, N) H2N-C=O Glutamine (Gln, Q) (H2N-C=O)-CH2 Cysteine (Cys, C) SH-CH2
Name the 3 basic* and 2 acidic* amino acids *at neutral pH
Lysine (Lys, K) NH3+-(CH2)*4 Arginine (Arg, R) 3(NH2)-C+ - (CH2)3 Histidine (His, H) imidazole-CH2 Aspartate (Asp, D) O-C-O - CH2 Glutamate (Glu, E) O-C-O - CH2 - CH2
What are the 2 acidic ionizable groups in proteins?
Terminal alpha carboxyls (Aspartic/Glutamic acid) Histidine
What are the 5 basic ionizable groups in proteins?
Terminal alpha amino groups Cysteine Tyrosine Lysine Arginine
What are the two resonance forms of a peptide bond? What is a consequence of this dipole on the atoms involved? What does that mean for the mobility of the amino acid as a whole?
N-C=O <-> +N=C-O-
Atoms involved are locked in a panar state
The aa has two rotatable bonds because of this on either side of the R group
What are the two confromations of a peptide bond?
Which one is more favored? When is that not the case?
Cis or trans
Trans is more favored (cis has too much steric hindrance)
X-Pro bonds have steric hindrance in either conformation and thus are found in equal populations
What are the phi and psi angles in a peptide? How can they be plotted? Why are there only so many combinations of angles?
R-C-C=O = Psi
R-C-C-N = Phi
Can be plotted via a Ramachandran plot, shows sterically possible conformations
What are the signs of the phi and psi torsion angles in an alpha helix?
What is the “handedness” of an alpha helix formed by L-amino acids?
How are alpha helices stabilized?
How does the alpha helix present its dipole?
Both negative torsion angles
L-amino acids form a right-handed helix
Stabilized between carbonyl O of residue i and amide group of i + 4
Strong dipole along the axis of the helix
Name a protein secondary structure that is not an alpha helix or a beta strand, and specify how it is stabilized
Turn
Most common is the reverse or beta turn
Stabilized by Hbonds between residues i and i + 3
What are the signs of the torsion angles in a beta strand?
Can this strand stand on its own? How is it stabilized?
Negative phi and positive psi torsion angles
Cannot stand on its own, stabilized by cross-strand H bonds (can be both parallel and anti-parallel)
When folding the secondary structure (forming the tertiary structure) what happens to the protein in order to stabilize interactions?
How do proteins begin folding?
A hydrophobic core is formed
Very tightly efficient, few empty cavities
Usually spontaneous process
Formation of intermediates, secondary structure forms very early on
Name and describethe 4 interactions that stabilize protein folding
Which one is less seen in the cytosol?
Hydrogen Bonding:
Between an electronegative X-H and a free electron pair Y: (don’t stabilize per se, unfavorable to produce)
Salt bridging:
hydrogen bond between two groups of full opposite charge
Van der Waals forces:
Maintains tight packing, relevant at close range
Disulfide bonding (less seen intracellularly due to reducing environment of cytosol): involves two cysteine side-chains
Describe the hydration shell.
Is the shell important?
Why can some water molecules detectable in crystal structures, whereas some aren’t?
A layer of bound water molecules on the surface of a protein
Integral part of structure, stabilized by hydrogen bonds
Some have unique positions (can be observed) while some are mobile and exhange rapidly
Why are aliphatic/aromatic side chains found inside protein folds whereas polar/charged side chains tend to face out of the protein?
To form H bonds with water molecules outside, compensating for the loss of entropy caused by ordered water molecules
Not the same as VdW forces
What are examples of non-protein stabilizers when a protein folds?
Metals (Zn finger motifs) and co-factors (heme)
What does the sum of all stabilizing interactions determine?
What can shift it?
What is a chaotropic agent and how does it affect it?
Range of stability: The map of pressure/Temperature combinations that the protein can withstand before denaturing
mutations in proteins can shift this range
Chaotropic agents (urea/guanidium hydrochloride) decrease the entropy of water and also denature the protein
What are chaperones and what are their two functions regarding protein synthesis?
What happens if these chaperones do not exist, or if hydrophobic side-chains are exposed?
Proteins that assist the folding of a protein by either allowing the protein to escape a trapped intermediate state (local minimum) or preventing the nascent protein from aggregating
Aggregation can occur from misfolded proteins
What are post translational modifications and their purposes?
Protease cleavage (activation/structural changes)
Ser, Thr, and Tyr phosphorylations which activates/inactivates proteins, induces new interactions, causes relocalizations or secretions
Lys or N-terminal ubiquitination, which can signal degradation or relocalization
Ser or Asn Glycosylation, which can induce secretion/refolding
Lys methylation/hydroxylation, N-terminal acetylation, acylation, lipidation, etc
What is the difference between an integral and peripheral protein?
What secondary strucutre is more prevalent in these membrane proteins?
What is another structure that is observed?
Integral - inside membrane
Peripheral - on surface
Alpha helices (with hydrophobic side chains interacting withnon-polar lipid chains) more common
Also Beta Barrels
What is the difference between orthologs and paralogs?
Orthologs: homologs that evolved from a common gene (eg pyruvate kinase in humans and E. coli)
Paralogs: evolved by gene duplication within the same genome (human Src and Abl kinases)
