Amino Acids and the Primary Stucture of Proteins

Important biological functions of proteins 1. Enzymes, the biochemical catalysts 2. Storage and transport of biochemical molecules

3. Physical cell support and shape (tubulin, actin, collagen)

4. Mechanical movement (flagella, mitosis, muscles) (continued)
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Globular proteins
Usually water soluble, compact, roughly spherical
Hydrophobic interior, hydrophilic surface

Globular proteins include enzymes,carrier and regulatory proteins

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Fibrous proteins

Provide mechanical support

Often assembled into large cables or threads a-Keratins: major components of hair and nails Collagen: major component of tendons, skin, bones and teeth

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General Structure of Amino Acids

Twenty common a-amino acids

A hydrogen atom and a side chain (R)

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Zwitterionic form of amino acids

amino acids zwitterions (dipolar ions):

Amino group = Carboxyl group = -NH3+ -COO-

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Stereochemistry of amino acids

Gly does not have a chiral -carbon

Threonine and isoleucine have 2 chiral carbons each

Mirror image pairs of amino acids are designated L (levo) and D (dextro) Proteins are assembled from L-amino acids

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Optical Activity
L D

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Four aliphatic amino acid structures

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Proline has a nitrogen in the aliphatic ring system

Proline (Pro, P) - has a three carbon side chain

heterocyclic pyrrolidine ring

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Aromatic amino acid structures

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Methionine and cysteine

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Formation of cystine

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Side Chains with Alcohol Groups

Serine (Ser, S) and Threonine (Thr, T) have uncharged polar side chains

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Structures of histidine, lysine and arginine

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Structures of aspartate, glutamate, asparagine and glutamine

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Basic Lys Arg His Polar Charged Lys Arg Glu Asp His Non-polar Gly Ala
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Acidic Glu Asp Cys Tyr

Uncharged Asn Gln Ser Thr cys Tyr

Leu Ile
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Val

Met

The Hydrophobicity of Amino Acid Side Chains

Hydropathy: the relative hydrophobicity of each amino acid The larger the hydropathy, the greater the tendency of an amino acid to prefer a hydrophobic environment Hydropathy affects protein folding

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 Hydropathy scale for amino acid residues

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Compounds derived from common amino acids

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Titration curve for alanine

Titration curves are used to determine pKa values pK1 = 2.4 pK2 = 9.9 pIAla = isoelectric point

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Ionization of Histidine

(a) Titration curve of histidine pK1 = 1.8 pK2 = 6.0 pK3 = 9.3

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Deprotonation of imidazolium ring

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pKa values of amino acid ionizable groups

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pKa values of amino acid ionizable groups

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Peptide Bonds Link Amino Acids in Proteins

Peptide bond - linkage between amino acids is a secondary amide bond Formed by condensation of the a-carboxyl of one amino acid with the a-amino of another amino acid (loss of H2O molecule) Primary structure - linear sequence of amino acids in a polypeptide or protein
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Peptide bond between two amino acids

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Polypeptide chain nomenclature

Amino acid residues compose peptide chains

Peptide chains are numbered from the N (amino) terminus to the C (carboxyl) terminus
Example: (N) Gly-Arg-Phe-Ala-Lys (C) (or GRFAK) Formation of peptide bonds eliminates the ionizable a-carboxyl and a-amino groups of the free amino acids
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Aspartame an artificial sweetener

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Amino Acid Composition of Proteins

Amino acid analysis - determination of the amino acid composition of a protein Peptide bonds are cleaved by acid hydrolysis (6M HCl, 110o, 16-72 hours)

Amino acids are separated chromatographically and quantitated

Phenylisothiocyanate (PITC) used to derivatize the amino acids prior to HPLC analysis
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Acid-catalyzed hydrolysis of a peptide

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Resonance structure of the peptide bond

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Planar peptide groups in a polypeptide chain

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Trans and cis conformations of a peptide group

Nearly all peptide groups in proteins are in the trans conformation

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There Are Four Levels of Protein Structure

Primary structure - amino acid linear sequence

Secondary structure - regions of regularly repeating conformations of the peptide chain, such as a-helices and b-sheets Tertiary structure - describes the shape of the fully folded polypeptide chain
Quaternary structure - arrangement of two or more polypeptide chains into multisubunit molecule
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a-helix

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Stereo view of right-handed a helix

All side chains project outward from helix axis

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Horse liver alcohol dehydrogenase

Amphipathic a helix (blue ribbon) Hydrophobic residues (blue) directed inward, hydrophilic (red) outward

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b-Sheets (a) parallel, (b) antiparallel

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Common motifs

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Common domain folds

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Quaternary structure of multidomain proteins

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Quaternary Structure
Refers to the organization of subunits in a protein with multiple subunits (an oligomer) Subunits (may be identical or different) have a defined stoichiometry and arrangement

Subunits are held together by many weak, noncovalent interactions (hydrophobic, electrostatic)

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Hemoglobin tetramer

(a) Human oxyhemoglobin (b) Tetramer schematic

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