Lecture 10: Protein building blocks Flashcards
What two factors determine the 3D structure, which dictates function of proteins?
polymer length
amino acid composition
Which is more complex - proteome or genome?
proteome
What residue is key in HIV-1 protease - Tipranivir interaction?
Asp26
What is the cause of Alzheimer’s?
42-residue fragment from Alzheimer precursor protein (SPP) is not cleaved to its normal 40-residue length
forms amyloid plaque
How many amino acids are deleted in cystic fibrosis?
one
What are three characteristics of each piece of a peptide and the order of connectivity which determine final shape?
- atomic bumping, backbone dihedral angles, secondary structure
- polar vs nonpolar
- charges, pKa
Why can’t a peptide bond be rotated?
partial double bond formed by N and C
What two things must happen for a protein to fold?
- rotate plates (atoms attached to C and N) to minimize clashing
- satisfy H-bond requirements of N and O on backbone
What angles determine final 3D structure of a protein?
phi
psi
What are the phi-psi angles of alpha helices and beta sheets?
alpha - ~0
beta - ~180
What does a ramachandran map show?
allowed phi-psi angles
grey regions are allowed
different AA favor different angles
Which amino acid has the largest grey area on a Rmacgandran map?
glycine (two H’s)
What is the pKa of Asp?
4.0
What is the pKa of Glu?
4.0
What is the pKa of His?
6.5
What is the pKa of Cys?
8.5
What is the pKa of Lys?
10.0
What is the pKa of Arg?
12.0
What is the pKa of the carboxy terminus?
4.0 (+ in cell conditions)
What is the pKa of the amino terminus?
8.0 (- in cell conditions)
What is an imino acid? Which molecule fits this description?
backbone N is not bonded to H
backbone N is bonded to its own side chain
Proline
What does Proline cause?
cis peptide bond
–> kink
Does a molecule with a high/low pKa bind H+ tightly/weakly?
high pKa - binds H+ tightly (basic)
low pKa - binds H+ weakly (acidic)
What is pKa?
pH at which 1/2 ionizing groups are protonated, half are deprotonated
What happens when pH < pKa?
ionizing group takes up h+ from solution
What happens when pH > pKa?
ionizing group gives off H+
What is special about histidine?
ionizes near pH 7
can both accept and donate protons at physiological conditions
What can be used to change pKa?
structure, environment
Under what conditions does Cys form the tiolate anon (–S-)
moderately alkaline (pKa 8.5)
Is the structure of a protein static or dynamic? Why?
dynamic
doesn’t get that much stability from folding
Do covalent interactions have a role in protein folding?
No
What four interactions have a role in protein folding?
electrostatics
H-bonds
van der Waals
hydrophobic effect
Where are charged groups usually found on a peptide? Give an example of a molecule
outside - interacting with water
ubiquitin
What is an example of a protein with a buried charge?
F0 proton channel of the F0F1 ATP Synthase
What two residues are essential for proton trasnport in the F0 proton channel of the F0F1 ATP Synthase?
Glu - proton binds
Pro - kink
Which - alpha helix or beta sheet - aligns peptide dipoles in parallel conformations? Is this favorable?
Alpha
Not favorable
How are polypeptides written?
N term –> C term
How is the peptide bond characterized? Why does it have this formation?
planar trans (except Pro) - avoid clashing between C=O groups
