PHAR 202 - Tertiary structure of a protein

What is a tertiary structure

it’s a 3D arrangement of folded secondary elements together with the spatial dispositions of its side chains

Globular proteins are compact true or false?

true

Globular proteins have a packing density, what is that?

it’s the ratio of the volume enclosed by the van der waals envelope of the atom in a region TO the total volume of the region

the packing density for globular proteins is 0.75, what does that mean when it folds

it means that when it folds it’s tight and stable

There are 3 types of amino acid residues, what are they?

• non polar residues

• charged polar residues

• uncharged polar residues

Where are non-polar amino acid residues found / occur?

• interior of the protein

• away from the aqueous solvent

Where are charged polar amino acid residues found?

• surface of the proteins

• they sometimes promote catalysis / metal ion binding

Where are uncharged polar residues found?

• protein surface but frequently occur in the interior of the molecule 

In the interior of the protein, there is an efficient packing due to Hydrogen Bonds. Nearly all buried hydrogen bond donos form hydrogen bond with….

burried acceptor groups

The formation of a hydrogen bond with a burried acceptor group ……… the polarity of the hydrogen bonding group (N—H or C=O)

neutralizes

Why is there efficient packing in the interior of the proteins

due to hydrogen bonds between burried acceptor groups and burried hydrogen bonding groups 

Why is ion pairing stronger in a protein in the interior but not the exterior

because it’s hydrophobic in the interior of the protein, the exterior has water on the protein surface that weakens ionic bonds, meanwhile proteins non-polar interior reinforces them

Which amino acid residues can make a salt bridge?

• (+) amino acids: histidine, lysine, arginine

• (-) amino acids: Glutamic acid, aspartic acid

Why can (+)/(-) amino acids form salt bridge

through their electrostatic attraction between their opposite charges along with hydrogen bonding between atoms within the charged groups

Hydrogen bonds are predominantly…….. between 

electrostatic interactions (but with 10% covalent character) 

acidic donor group and an acceptor than has a lone pair 

Hydrogen bonds only weakly stabilize proteins, but provides….

a structural basis for its native folding pattern

In low medium (low dielectric constant), the E of the hydrogen bonding is…

-3 to -7

What force is a major influence in determining protein conformation

London Dispersion Force

What is the difference between permanent dipole and induce dipole

Permanent dipole

• permanent separation of charge in molcues 

• lasting positive and negative end

Induced dipole

• temporary separation of charge form when an external electric field distorts the electron cloud of a neural molecule

• momentary positive and negative end 

what is pi-pi stacking

when amino acids preferentially align their benzene rings

is pi-pi stacking weaker than LDF?

yes, but they are significant in controlling protein conformation and substrate binding properties

what is cation-pi interaction

when the cation attracted to negative electrostatic potential of a benzene ring (happens every 77 amino acids in PDB)

What is the hydrophobic effect

non-polar susbtances minimize their contacts with water + amphipathic molecules

why is the hydrophobic effect important in determining protein structure

because native proteins form an intracellular micelle

Why does transferring a hydrocarbon from water to a nonpolar solvent increase entropy (ΔS > 0)?

• Water molecules form an ordered "cage" around them (low entropy).

• If the hydrocarbon leaves water, the ordered water cage breaks → water becomes freer → entropy increases (ΔS > 0).

What is the enthalpy change (ΔH) for aliphatics when transferred from water to nonpolar solvent?

Positive (endothermic).

What is the enthalpy change (ΔH) for aromatics in the same transfer?

Approximately zero (athermic).

Is the hydrophobic effect mainly driven by enthalpy or entropy?

By entropy (ΔS).

What drives the spontaneity (negative delta G) of the process

the larg TAS component which is entropically driven due to the hydrophobic core collapsing 

What is Clathrate

ordered water molecules (a water cage) that surround a nonpolar solute

Explain this diagram

• bars above: protein interior

• bars below: protein exterior

• as it goes up (+), it’s more hydrophobic

• as it goes down (-), it’s more hydrophilic