S1 - Proteins + folding Flashcards
What are proteins?
- Polypeptides
- macromolecules made up of AA’s joined covalently
- the polypeptide chainf olds into a complex 3D structure determined by sequence of AA
What does the folding of proteins depend on?
chemical and physical properties of AAs
What is the general structure of an amino acid?
- Central carbon atom (alpha) covalently bonded to:
- -> An amino group (NH2)
- -> carboxyl group ( -COOH)
- -> hydrogen atom
- -> a distinctive R group (side chain)
How are amino acids classified?
According to the properties of their R groups:
Chemical properties:
- Hydrophobic (hates water) or hydrophilic (likes water)
- polar or non polar (polar are charged or can H bond)
- acidic, basic or neutral
Physical properties:
- Aliphatic (straight chain) or aromatic (benzene ring)
What is an AA residue?
What remains of an AA after it has been joined by a peptide bond to form a protein
a) How do AA’s NORMALLY act at physiological pH and why?
b) What does the pKa value of an AA side chain tell you about that chemical group?
a) As their zwitter ion (positive and negative charges) with no overall net charge as there is a reaction between acid and basic groups.
b) Measure of acid strength- how likely the molecule is to take the proton from solution or donate a proton to the solution
a) When comparing pH and pKa values what do you need to keep in mind?
b) If the pH of a solution is higher than the pKa of a side chain what will happen?
c) if the pH of a solution is lower than the pKa of a side chain what will happen?
a) - pH of solution and pKa of molecule (side chain)
- the higher value has the stronger desire for the proton and takes it away from the other
b) the solution wins i.e. the solution will take the proton from the molecule and the molecule will be deprotonated
c) the molecule wins i.e. the molecule is stronger and therefore the molecule takes the proton away from the solution and the molecule will be protonated!
How do a) acids and b) bases normally act?
a) normally donate h+
b) normally accept h+
a) What is the isoelectric point (pI) of a protein?
b) What does it mean if the pH is i) smaller or ii) bigger than the pI of a protein
a) The pH at which there is no overall net charge
b)
i) pH < pI: protein is protonated
ii) pH > pI: protein is deprotonated
a) Explain why some AA side chains are charged at physiological pH?
b) how do you calculate the relative proportions?
a) - Most AA have a net charge of 0 at physiological pH as there is a reaction between acid and basic groups balancing the charge out
- if the pKa of side chains are higher or lower than the physiological pH then the side chain will become protonated or deprotonated hence carrying a charge
b) Using the henderson-hasselbach equation
At physiological pH, the side chain of aspartic acid has a pKa value of 2.8. What does this mean?
- pH =7ISH
- pH > pKa and so the side chain will become deprotonated and carry a negative charge
The protein serum albumin has an isoelectric point of 5.0. If this protein was placed in an electric field at physiological pH, would it move towards the positive or negative electrode. Explain?
- pH > pI
- Protein would become deprotonated (lose proton to solution)
- carry a negative charge and hence it would move towards the positive electrode
What is the: a) primary structure b) secondary structure c ) tertiary structure d) quaternary structure
of a protein
a) the linear AA sequence in a polypeptide chain held together by peptide bonds
b) Folding/coiling of the primary structure due to H bonding between AA carboxyl groups –> leads to spatial arrangements e.g. alpha helixes or beta sheets
c) Further folding/coiling of the chain into a 3D shape due to bonds between r-groups
d) association between different polypeptide chains to form a multi-subunit protein
a) How are peptide bonds formed?
b) Properties of peptide bonds
c) What is the Psi (ψ) peptide bond?
d) What is the Phi (φ) peptide bond?
e) Why is the AA in proteins so important!
a) linking of two AA’s via condensation reaction (abstraction of water molecule)
b)
- planar (lie in the same plane)
- rigid (C-N has partial double bond cxtics and unable to rotate which contributes to polarity)
- fixed in either a cis or trans configuration due to lack of rotation (mostly in trans where: Cα atoms are on opposite sides of the peptide bond)
- bonds on either side of the peptide bond are free to rotate
c) Cα- C bond
d) Cα- N bond
e) determines the way in which the polypeptide chain folds and its physical cxtics
For the secondary structure what is the features of the:
a) alpha helix
b) beta pleated sheet
a)
- 3.6 AA residues/ turn
- 0.54 nm pitch (vertical distance of 0.54nm between residues)
- right handed helix
- the backbone C=O group of one residue is h-bonded to the -NH group of the residue 4 AA’s away
b)
- fully extended conformation
- formed by H bonds between protein strands rather than within a strand
- 0.35 nm between adjacent AA
beta CAN BE:
i) antiparallel: adjacent B-strands run in opposite directions (more stable as more interstrand H bonds)
ii) parallel: adjacent strands run in the same direction (less H bonds)
Iii) both
