PROTEIN PHYSICS

LECTURE 10

Protein chain: gene-encoded

sequence of side-chains,regular main-chain

Ala _L_ Ala -D-

Glysymmetric

ALL THE OTHER: ASYMMETRIC BACKBONE

Two amino acids have asymmetric side chains:

Chemical S-S bond of two CYS side chains:

THR

ILE

The 20+2 amino acidsGlycine Methionine(e) Tyrosine

Alanine Tryptophan(e) Arginine(e)

Valine(e) Cysteine Histidine(e)

Isoleucine(e) Serine Lysine

Leucine(e) Threonine(e) Glutamic Acid

Phenylalanine(e) Asparagine Aspartic Acid

Proline Glutamine

Selenocysteine Pyrrolysine

Encoded by UGA,SECIS required

Encoded by UAG,PYLIS required

Hydrophobic

Negatively charged

Positively charged

Polar uncharged

(e) – essential amino acids

Glycine Methionine Tyrosine

Alanine Tryptophan Arginine

Valine Cysteine Histidine

Isoleucine Serine Lysine

Leucine Threonine Glutamic Acid

Phenylalanine Asparagine Aspartic Acid

Proline Glutamine

Prefer alpha helices: cover and protect the backbone H bonds

Prefer beta sheets: amino acids with large, bulky side chains

Prefer loops and turns: disrupt helices and sheets

Structural Occurrence Tendency (I)

Reference: protein course from Helsinki

N – terminal turn

C – terminal turn

just before

just after

In beta Sheets

In loops

In alpha helix

In the hydrophobic core

Thr, Ile, Val, Leu, Met, Phe, Tyr, Cys, Trp

Gly, Pro, Asp, Asn, Ser, Arg

Ile, Val, Leu, Met, Phe, Tyr, Cys, Trp

Glu, Asp, Asn, Ser, Thr

Ala, Pro, Glu, Asp

His, Lys, Arg

Asn, His, Lys, Arg

Leu, Met

Ala, Ile, Val, Leu, Met, Phe

Glu, Asp, Gln, Asn, Ser, Lys, Arg,

Gly, Pro, Glu, Asp, Asn, Lys, Arg

Pro, Asp, Asn,Tyr, Cys

Lys, Arg

Gly, His, Lys, Arg

Pro, Glu, Asp

Pro, Glu, Asp Structural Occurrence Tendency (II)

Glycine Proline

• its ability of H-bonding is halved

• only close to the N-terminus of alpha helix

• tends to bend/causes kinks/break helices

• its phi ~ 60°, pretty much restricted,corresponding to alpha helices

• its psi ~ -45°, 135°, corresponding to sheets

• not preferred in sheets, maybe in bulge or sheet edge,

• tends to disrupt the helix, it is entropically expensive state

• prefers irregular segments

• destabilizing residue in sheets

H-bonding side chains compete directly with backbone H-bonds

Asp, Asn, Ser

Cysteine Methionine

• hydrophobic side chain, its S atom is not reactive

• highly reactive sulfhydril (thiol) group, which causes disulfide bridges

Disulfide Bond

• In proteins the reaction is catalyzed by disulfide isomerase

• Unstable in the cytoplasm, important for proteins that reside and function out of the cell

CH2

CH2

CH2

SH + HS CH2

S + 2HS

GSH – monomeric thiol

GSSG – dimeric disulfide

Ionized Side Groups

Increasing pH shifts the charged state of a group “in the negative direction”

For an ionizable group is easier to penetrate into a non-polar medium in its uncharged form than in its charged one. After that it just gets charged.

typical of proteins in a living cell

Tendencies

• Hydrophobic residues and residues with large side chains prefer sheets

• Amino acids with polar side chains prefer irregular surface region, where they can easily participate in H-bonds with both the chain and water

• Negatively charged amino acids prefer the N-terminus of the helix, and they avoid the C-terminus. The preference of positively charged amino acids is opposite.

• Polar side chains prefer to be on the protein surface, in contact with water.

• Hydrophobic side chains prefer to be in the interior of the protein.

polar

non-polar

• S-S bond may form the nucleus of the hydrophobic core

non-polar: corepolar: surface

non_polar: in the corepolar: at the surface

−Half-charged: active sites

pKa||

pKa||||

Pcharged / Puncharged

= 10−(pKa – pH)

Acids (charge −) Bases (charge +)

Pcharged / Puncharged

= 10+(pKa – pH)

Pcharged + Puncharged = 1

charged −: coil, α_Ncharged +: coil, α_C

−Half-charged: active sites