(Proteins and Enzyme) Protein Structure 2

describe the geometry of a 3_10 helix

H bond every 3rd AA reside, tightly coiled helix

describe the geometry of a 𝝅-helix

H bond every 5th AA residue, loosely coiled helix

why are tightly coiled helices more sterically unfavourable than loosely

Tightly coiled helices are more sterically unfavourable because they distort φ/ψ angles, increase side‑chain clashes, and weaken H‑bonds. Loosely coiled helices stay in low‑energy conformations.

what is the significance of enzymes having a 𝝅-helix in between the 2 pockets where substrates fit ?

helix can collapse and rebuild H bonds aiding substrate shuttling

what is the result of the partial charges of side chains reinforcing the strength of the helix structure ?

crates a partial positive charge at the N-terminus and a partial negative charge at the C-terminus

what is the effect of the helical dipole on enzymes ?

attracts substrates

on an α-helix bulky residues or same charged residues cause __________ _______________ which reduces stability

steric repulsion

If there are 2 oppositely charged residues near each other then a _______ ____________ is formed (attracts residues on the same face of the helix)

salt bridge

why does the F helix on the EF hand motif tend to be different lengths ?

if the AA 3 residues apart are the same charge, they repel each other and the protein cannot fold into a helix

why does proline cause kinks/breaks in an α-helix ?

the free NH is lost in the peptide bond and it loses the ability to make H bonds

what is the effect of the proline cis ⇌ trans conversion slowing down protein folding rate ?

Proline can adopt both cis and trans peptide bonds, but interconversion is very slow, creating misfolded kinetic traps. Prolyl isomerases accelerate cis-trans switching, allowing proteins to escape misfolded intermediates and fold correctly.

polypeptide plane twists can be favourable and unfavourable, what planes can you twist around?

𝛟 bond (between the N of amide and C of side chain) and the 𝛙 bond (between the C of the side chain and C of the carboxyl group)

what do outliers in the ramachandran plot tend to mean ?

tells you protein structure has been warped and it is likely a residue involved in an active site

what is the difference between the PP1 proline helix and the PP2 proline helix ?

PP1 is more tightly wound, PP2 is a looser more meandering helix

describe the structure of collagen

3 let handed helices join to form a right handed supercoil - hydroxyproline at the centre binds water to stabilise collagen

transmembrane helices do not often exist in isolation - what do they bundle together to form?

a 4 helical bundle

how do the differences in loops allow helices to run parallel and antiparallel to one another ?

tight turns allow antiparallel helices while longer loops allow parallel strands

α-helical arrangement of side chains allows the formation of ridges and grooves (side chains outwards forms a ridge) what is the angle between the i:i+3 helix and the i:i+4 helix ?

45º and 25º respectively

2 helices that both have a 25º angle fit so they are 50º apart, where is this type of fold found ?

in the globin fold

2 helices, one with a 25º and other with a 45º will fit so that the ridges are only 20º apart, where is this angle of helix found ?

in the tighter structure of the 4-helix bundle

describe the geometry of the coiled-coil motif

each helix has a heptad repeat pattern, hydrophobic residues are 3 AA apart

what is the biological role of the coiled-coil structure?

Sit in groove of DNA and controlling transcription by selective dimerisation

what factors determine the angles between helical axes ?

- AA sequence

- helix length

- surrounding environment

evolution exists to maximise economy - what difference can you see between proteins that stay inside the cell and proteins that are outside the cytoplasm?

proteins recycled within the cell are more 'expensive' to make than those outside

proteins can often have 2 possible conformations (whether substrate is bound or not) - what is the idea of metastability that comes with this ?

both states of protein have to be stable and achievable

Take 2 small proteins PSD1 and GB1 - take the sequence of both proteins and put into a sequence alignment - will see some conserved AA. Can mutate the rest of the sequence (keeping conserved AA the same) to have 2 proteins that have an 88% sequence identity but fold as 2 different proteins, what does this allow you to see ?

where mutated protein differs shows you regions that are key in protein folding

proteins fold like string which means they can be knotted - what is the effect of protein knotting ?

proteins are more resistant to proteases

what is the 'fit data' in modelling proteins?

building a model that fits experimentally observed data

what is the theoretical data in modelling proteins ?

can theorise how the primary sequence folds into the secondary structure

what is the comparative data in protein modelling ?

comparing sequences with other known folds

how will a longer polypeptide be produced from a circular RNA ?

translation will likely skip a reading frame - translate circle 3 times before stop codon is reached

what does coulombs law state ?

like charges repel and opposite charged attract

what does lennard-jones law state ?

attractive forces are stronger at longer distances while repulsive forces are significant when molecules are close

explain how mutations would have to co-evolve

mutation at one point causes a mutation elsewhere otherwise AA charged would attract or repel

how does looking at AA mutations over time allow you to predict protein structure ?

you know those that have mutated that have mutated together must interact in the folded protein

explain how alphafold works to be very effective in creating proteins

ai used to generate protein structures from noise rather than a data set