protein structure & function Flashcards
What is primary structure of polypeptide ?
sequence of amino acids
polypeptides-unbranched polymers of amino acid residue which are linked togwther by the ribosome
-primary structuyre looks like this :ABFDIKHF
this sequence adopts certain 3D structure detemining reactivity
What are proteins made from ?
made from L-amino acids
-S enantiomers (unless cysteine)
-polypeptide 3D strcutures begins with the atomic position around backbone -backbone generously
Peptide bonds
cant rotate
typicaly trans configuration
180 between H & O
How can we describe backbone geometry ?
with 2 torsion angles
only peptide bond that is fixed
atoms around other 2 bonds can adopt diff conformations
phi adn psi angles
What angle is the phi angle ?
between the successive backbone carbonyl atoms ?
What angle is the Psi angle ?
between succesive backbone nitrogens
why are some values of phi and psi more stable than others ?
phi is unlikely to be zero
-steric repulsion between bulky groups
common recurring combinations are particularly favoured by hydrogen bonding
-see in ramachandran plot
what is a ramachandran plot ?
visualizes energetically allowed and forbidden regions for the dihedral angles
Beta sheets are what ?
psi is near 180; 3.5 Å between residues
e.g:antiparralell beta sheet
A-helix and blah ?
more compact structure
“i + 4–>i” hydrogen bonding
-3.6 residues/turn
-1.5 Å between residues
-Hairpins (B) turn between helices stabilised by i + 3—> hydrogen bonding
What do different amino acids prefer ?
differents econdary structures
1. Pro-disrupts a-helices and B-sheets
2. Gly & Pro are comman in B-turns ,although Gly can adopt many psi and phi angles
3. Bulkier,hydrophobic sidechains-Val,Ile tend to favour B-sheets
4. Ser,Asp,Asn sidechains tend to disrupt a-helices
What is a tertiary structure ?
overall 3D structure of polypetide
-involves the precise positioning of secondary structural units
-tertiary structure is stabilised by
non-covalent interactions
disulphide bridges
What are loops ?
random coils used as flexible binding sites in many proteins
-antibodies can bind antigens strongly loop regions
very low dissociation constant
some (many )proteins are mostly disturbed until they bind to a partner
Define Structural protein ?
proteins may form insoluble extended structures by bonding to themselves
What are binding & transport proteins ?
proteins may bond with other molecules at their binding sites
eg.)myoglobin,haemoglobin
Define catalytic proteins ?
proteins may bond with transition states at their active sites to increase reaction rates
1st example of of structural protein ?
α Keratin-main componant of hair,epidermis & fingernails
-fibrous,insoluble structure based on RH α-complex
-these helices are coiled together in a long left-handed super-helix
How do keratin α-helices bind to each other ?
helix is slightly distorted :3.5 residues / turn
every 7th residue is similar position in helix
chosen to bind non-covalently with one another – hydrophobic effect important
-“heptad repeats “
-helices also attached covalently via disulphide bonds
HAIR STINKS WHEN BURNED
2nd example of structural protein ?
Collagen
-main component of connective tissue in mammals
-tendon,cartlidge & dermis
long-triple helix
near β-sheets in ramachandran plot
-Vanderwaals interaction within helices & hydrogen bonds between helices
-every 3rd residue-glycine-make helix compact
proline and hydroxyproline are comman too
What is the collagen triple helix ?
Gly is small enough to fit in helix centre
-Hyp also stablises structure by using its hydroxyl group to form inter-strand hydrogen bonds
-hyp synthesis depends on vitamin C (ascorbate)
What is protein pathological aggregation ?
water soluble proteins may mis-fold and bind to 1 another to form insoluble fibres
eg.)amyloid fibrils in alzheimers ,type 2 diabetes & prion diseases
How do enzymes work ?
-proteins are biological catalysts
-they lower the energy barrier(Activation energy) on a reaction
speeds it up
What do enzymes do to transition states ?
stabilise them
transition state-highest energy structure on reaction pathway
a reaction may happen in diff ways with diff transition state
enzymes provide reaction pathway with lower energy TS
enzymes bind to TS to catalyse reaction
active site forms bonds with TS2
release energy and therefore stabilises transition state
Serine proteases & hydrolysase stabilising -vely charged TS
TS for this step develops negative charge on carbonyl oxygen
oxyonion hole stabilises charge with 2 hydrogen bonds
reaction goes fast
