5.2, 6.1 Protein Structure And Function, clinical context Flashcards
What is the general structure of an AA?
Carbon with attached carboxyl group, amine group, Hydrogen and R group
NH2 H-C-COOH R
What would be the general structure of AA in the following three solutions
1) Acidic (low pH)
2) Neutral
3) Basic (high pH)
1) acidic so more H+ ions so NH2 which is a proton acceptor becomes NH3
2) zwitterion, NH3 and COO-
3) COOH group is a proton donor so COO-
How can you differentiate AA from each other?
By their chemical and physical properties of R groups
- hydrophobic/philic
- Polar/non-polar
- Acidic/basic/neutral
- Aromatic/aliphatic
What is pKa?
pKa = -log10(Ka)
Where Ka is the acid dissociation constant
Tells us strength of acid/how likely grps are to loose/gain proteins
Fill in the gaps
Smaller the value of Ka, _______ the value of pKa, _______ extent of dissociation, ________ the acid, H+ _______, more _______
Larger, smaller, weaker, acceptor, NH3+
Fill in the gaps
Larger the value of Ka, _______ the value of pKa, _______ extent of dissociation, ________ the acid, H+ _______, more _______
Smaller, larger, stronger, donor, COO-
Explain what happens when pK of AA > pH of solution.
pK larger so weaker acid so proton acceptor so more NH3+
I.e. R group protonated
Explain what happens when pK of AA < pH of solution.
pK smaller, so stronger the acid, proton donor, so more COO-
I.e. R group deprotonated
Negatively charged R groups have a lower/higher pK?
Positively charged R groups have a lower/higher pK?
More COO- so proton donor so more acidic so pK smaller
More NH3+ so proton acceptor, so less acidic so pK larger
What bond holds amino acids together?
Peptide bond - O=C-N-H
How is the peptide bond rigid if there is a single bond between the Carbon and Nitrogen?
It carries partial double bond characteristics
(O-)-C=N-H is in equilibrium with O=C-(N+)-H
Does the peptide bond exhibit cis or trans conformation, and why?
Trans
Calphas are on opp sides of bond
Cis conformation not favourable because of steric clashes (repelling)
What bond is present in primary structure of proteins?
Peptide/covalent hold primary structure together
What are the secondary structures of a protein and how are they determined?
Determined by angles of C-Calpha and Calpha-N
- Alpha helix
- Beta sheets
How is the alpha helix formed and which AA are good/bad at forming these?
H bonds between N-H and C=O 4 AA away
Small hydrophobic residues are strong helix formers
Big not so good
How is the beta sheet formed?
Side by side strands run
1) antiparallel stabilised by H bonds
2) parallel - different angles so weaker
3) mixed antiparallel and parallel
Describe 3 types of tertiary structure and bonds present
3D configuration of protein
Fibrous Role - support, shape, protection Long strands/sheets Single type of repeating structure E.g. Collagen
Globular
Role - catalysis, regulation
Compact shape
Several types of secondary structure
Water soluble
Role - membrane proteins
Polypeptide chain folds so hydrophobic side chains are buried
Polar chains on surface
Bonds - covalent, ionic, H bonds, van der waals, hydrophobic/philic, disulphide
Describe a quarternary structure
When 2 or more proteins become held together e.g. Haemoglobin/ribosome
What is pI?
- Isoelectric point
2. pH at which molecule carries no net electrical charge
What is the pI of basic proteins?
pI>7 and contains many charged AAs (NH3+)
What is the pI of acidic proteins?
pI<7 and contains many negatively charged AAs (COO-)
What happens if pI of AA < pH of solution?
More acidic so proton donor so R groups would be deprotonated
What happens if pI of AA > pH of solution?
More basic, proton acceptor, so R groups would be protonated
What does the henderson hasselbach equation used for?
Calculate the pH of a buffer solution
pH = pKa + log (base/acid )
What happens to the AAs when pK =pH
Equal amounts of protonated and deprotonated forms
What AAs are covalent disulphide bonds made between ? Where are these proteins most commonly used?
Cysteine residues
Usually secreted e.g. To go to pancreas which has a hostile environment so need strong bonds holding it together
What are electrostatic interactions formed between?
Charged groups e.g. Glu-, Arg +
What are hydrogen bonds made between?
Electronegative atom and a hydrogen bound to another electronegative atom
What are van der waals forces made between?
Dipole - dipole
What is the hydrophobic effect?
Interaction between hydrophobic side chains due to displacement of water
What is the name given to a normally folded protein that is functional?
In native conformation
What is denaturation and how does it occur?
Disruption of protein structure through breaking forces holding it together
E.g by heat, pH, organic solvents affecting hydrophobic interactions
What is the folding process of an amino acid sequence driven by? How does it do this without taking too long?
Need to find the most stable conformation
Each step involves localised folding with stabilised conformations maintained
What are amyloidases?
- Misfolded, insoluble form of a normally soluble protein.
- Hence forms aggregates in tissues and organs throughout the body
- Causes tissues and organs to stop working properly
Note - the point of this is to note that protein misfolding can cause disease!
