Building Blocks of Proteins – Amino Acids, Peptides & Peptide Bond

Learning Objectives

  • Relate amino-acid chemistry to protein structure/function
  • Identify side-chain types & their key chemical features
  • Describe peptide-bond formation & properties

General Amino-Acid Structure

  • Common backbone: H<em>2N!!−C</em>α(H)(R)−COOHH<em>2N!!{-}C</em>{\alpha}(H)(R){-}COOH
  • Features: amino group, CαC_{\alpha} with hydrogen + side chain RR, carboxyl group
  • Exist in solution as zwitterions: +H<em>3N−C</em>α(H)(R)−COO−^{+}H<em>3N{-}C</em>{\alpha}(H)(R){-}COO^{-} at physiological pH
  • Chirality: L-form used in proteins (except achiral Gly)

Amino-Acid Nomenclature

  • Each residue has: full name, 3-letter code, 1-letter code
  • Mutation shorthand: E6VE6V (native, position, variant)

Classification of Side Chains (at pH ≈7\approx 7)

  • Non-polar (hydrophobic): Ala, Val, Leu, Ile, Met, Phe, Trp, Pro, Gly
    • Prefer interior of proteins
  • Polar uncharged (hydrophilic): Ser, Thr, Asn, Gln, Tyr, Cys
  • Charged
    • Acidic (−): Asp, Glu
    • Basic (+): Lys, Arg, His
  • Special cases: Gly (flexible, non-chiral), Pro (rigid imino acid)

Ionisable Groups

  • Terminal α\alpha-COOH & α\alpha-NH_3^{+} always ionisable
  • Some side chains ionisable; pKa governs charge state
    • Acidic: pK_aAspAsp\approx 3.9,Glu, Glu\approx 4.3
    • Basic: Lys \approx 10.5,Arg, Arg\approx 12.5,His, His\approx 6.0
    • Others: Cys \approx 8.3,Tyr, Tyr\approx 10.1
  • Isoelectric point pI:pHwherenetcharge: pH where net charge=0

Peptide Bond & Peptides

  • Amino acids join via condensation → peptide bond CO{-}NH
  • Properties
    • \sim 40\% double-bond character ⇒ planar & rigid
    • Predominantly trans configuration
    • Possesses dipole (partial +Ntoto−O)
  • Peptides: <\sim 50 residues; proteins: larger polypeptides with function
  • Residues numbered from N(amino)→(amino) →C (carboxyl) terminus

Post-Translational Modifications (PTMs)

  • Occur after ribosomal synthesis; diversify function
  • Key types & roles
    • Phosphorylation (Ser, Thr, Tyr) – enzymatic ON/OFF switch
    • Hydroxylation (Pro, Lys) – collagen stability; vitamin C dependent
    • Carboxylation (Glu) – blood clotting (binds Ca^{2+})
    • Disulfide bond (Cys–Cys) – structural stability
    • Glycosylation (Asn, Thr, Ser) – cell recognition, stability
    • Metal binding, iodination, others

Quick Recall Checklist

  • Backbone sketch?
  • 1- vs 3-letter codes?
  • Definition of chirality?
  • Four side-chain classes?
  • Non-polar residue location?
  • Common ionisable R-groups?
  • Typical peptide-bond traits?
  • Meanings of pK_a & pI$$?
  • Examples & functions of PTMs?