Amino Acid|Graduate Biochemistry 2| Tulane

Overview

Protein Structure

• Proteins are polymers of amino acids
• Native proteins are folded into a unique three dimensional structure
• The three dimensional structure is responsible for specificity and biological activity
• The structure is determined entirely by the primary sequence of amino acids through the physical & chemical properties of the amino acids

Amino Acid Properties

• Chemical Structure
• R group is variable
• 20 amino acids are found in proteins

• Amino acids are chiral (optically active)
• Amino acids in proteins always have the L configuration (Equivalent to the configuration of glyceraldehyde that rotates polarized light to the left)
• Levorotatory – Leftward rotation of light
• Dextrorotatory – Rightward rotation
• L amino acids are not all Levorotatory

20 AA

Remember the abb. and name and groups of all amino acids

Gly	G	Glycine	Glycine is in the β turn
Ala	A	Alanine	Every where -> hydrophobic but not really strong
Val	V	Valine	hydrophobic, strictly in shape
Leu	L	Leucine	…
Ile	I	Isolucine	β branched
Met	M	Methionine	containing sulfate, hydrophobic
Pro	P	Proline	tight turn
Phe	F	Phenylalanine
Tyr	Y	Tyrosine	Phenylalanine-(OH)
Trp	W	Tryptophan	largest hydrophobic group
Asp	D	Aspartate	β Carboxyl
Glu	E	Glutamate	γ Carbocyl
Lys	K	Lysine	ε Amino Group
Arg	R	Arginine	γ Guanidino Group
His	H	Histidine	β Imidazole Group
Ser	S	Serine	&beta hydroxyl
Thr	T	Threonine	hydroxyl gorup
Asn	N	Asparagine	Amide Group; Can not accept proton
Glu	Q	Glutamine	Amide Group; Can not accept proton
Cys	C	Cysteine

Properties:

• Aliphatic (hydrophobic)
• Secondary Structured
• Aromatic (hydrophobic)
• Charged
• Polar, uncharged

Ionization Properties of Amino Acids

AA	Function Group	pKa
Asp	-CH2-COO-	3.9
Glu	-CH2-CH2-COO-	4.3
Lys	-CH2-CH2-CH2-CH2-NH3+	10.8
Arg	-CH2-CH2-CH2NH-C(-NH2)=NH2+	12.5
His	-CH2-Imidazole	6.5

primary structure

1. Direction: N -> C
2. Average molecule weight of per amino acid is ~110.

Properties of the Peptide Bond

• Electronic resonance gives the central -C(=O)N(H)- atoms some double-bond character
• Double bond character gives these bonds a generally planar (not tetrahedral) shape and rigidity
• Coplanarity severely limits the number of accessible conformations

Cis-trans isomerization

• Trans peptide bonds are energetically preferred
• Cis peptide bonds are rare:
  • 0.05% of all non-proline peptide bonds are cis
  • 6.5 % of all X-Pro peptide bonds are cis
• Rate of conversion between cis and trans is slow

Trans: opposite
Cis: same side

Conformational Properties of Polypeptides

• Protein backbone conformation can be described with 2 torsion angles Phi (Φ) and Psi (Ψ) around Cα
• Steric clashes make only some combinations of Φ and Ψ permissible
• The requirement for hydrogen bonding between backbone groups in folded proteins further limits the observed values for Φ and Ψ

$\phi$	$\psi$

Ramachandran Plot © HarvardX

© Sepp Hochreiter

Secondary Structure of Polypeptides

• Hydrogen Bonds are weak noncovalent interactions between polar groups.
• In a folded protein, backbone groups are always involved in hydrogen bonds.
• Hydrogen bonding along with the allowed φ , ψ torsion angles determine the possible types of secondary structure

• Secondary structure is the local conformation the backbone
• Secondary structure is defined by Hydrogen bonding patterns and Φ , Ψ torsion angles

α helix

© PDB ID=1SI4

• Right handed helix
• Interactions are local
• Defined by Hydrogen-bonding pattern (ith) C=0 - - - NH (i+4)th
• Accounts for well more than half of all protein structure
• Pitch: 3.6 residues per turn
• Rise: 1.5 Å per residue (5.4Å/turn)
• 13 atoms in the hydrogen bonded loop

Hemoglobin - an all α helical protein

Close packing in an α-helix

• Helices are very tightly packed structures
• The C=O::HN hydrogen bonds are partially buried within the core of the helical structure
• Because of steric constraints and hydrophobic interactions between side chains, the amino acids have very different propensities for being in an α-helix.

The β-pleated sheet

© PDB ID=2QLE

• Chains are extended
• Interactions are nonlocal
• Can be parallel or antiparallel
• Antiparallel is preferred
• Can contain from 2 to 25+ strands
• Accounts for most non-helical protein structure
• Length: 3.3 Å per residue

Influenza Neuraminidase an all β-sheet protein

Reverse Turn

• Short 180º turn of ~ 4 residues
• Connects elements of secondary structure
• Interactions are local
• Often occur at surface of protein
• Many types are defined by hydrogen-bonding patterns

The hairpin motif

others

3-10 helix

• Uncommon right-handed helix
• Hydrogen-bonding pattern:
  C=0 (i) - - - NH (i+3)
• Often found at the ends of α-helices

π helix

• Rare right-handed helix
• Hydrogen-bonding pattern:
  C=0 (i)- - - NH (i+5)

Ω loop

• Found at the surfaces of proteins
• Base of loop is part of a proteins secondary structure, while the loop is disordered as in the letter omega (Ω )

Random coil

• No regular secondary structure
• Highly flexible

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• Portein

• Folding collapse;

  • Mostly drived by hydrophobic
  • hydrogen binding group are fold in the core of the protein

• Visual

  • Schematic; Ribbon diagram; Cα trace; CPK space-filling; Solvent-accessible surface

• Structure of protein

  • Secondary; Tertiary; Quaternary

• Anfinsen-Merrifield experiments

• Evolution in sequence

• protein motif

• β-sandwich

• coiled-coil

• EF hand

• Domain structure of large proteins

• Quanternary structure of protein

Protein Folding

Levels of Structure

Exp: Ribonuclease A; 124 residues; 4 disulfide bonds; Unfolded with denaturants (1. urea or guanidine; 2. Oxidase/reduce the disulfide bound.)

Structure motif

• $\beta \alpha \beta$
• $\alpha \alpha \alpha$
• $\beta \beta$
  …

Tim-brrel: ($\beta \alpha \beta \alpha$)₄