Biochemistry - Structure, Properties of Amino Acids PDF

Structure and properties of amino acids. The peptide bond.  Structure and properties of amino acids. The peptide bond. 1. Amino acids: structure and classification 2. Acid-base properties 3. Peptides and proteins 4. Characteristics of the peptide bond 1. Amino acids: structure and...

Structure and properties of amino acids. The peptide bond.  Structure and properties of amino acids. The peptide bond. 1. Amino acids: structure and classification 2. Acid-base properties 3. Peptides and proteins 4. Characteristics of the peptide bond 1. Amino acids: structure and classification Proteins are polymers of amino acids In every living organism, proteins are constructed from a common set of 20 amino acids. Each amino acid has a side chain with distinctive chemical properties. Amino acids may be regarded as the alphabet in which the language of protein structure is written. Asparagine (1806) Threonine (1938)  Amino Acids Share Common Structural Features ± carbon and four substituents ± carbon is the chiral center tetrahedral Nomenclature: 3-Letter and 1-letter codes 1. Unique first letter: 3. Similar sounding names, structure: Cysteine Cys C Arginine Arg R Histidine His H Asparagine Asn N Isoleucine Ile I Aspartate Asp D Methionine Met M Glutamate Glu E Serine Ser S Glutamine Gln Q Valine Val V Phenylalanine Phe F Tyrosine Tyr Y 2. Most commonly occurring Tryptophan Trp W amino acids have priority: Alanine Ala A 4. Letter close to initial letter: Glycine Gly Lysine Lys K G Leucine Leu L Proline Pro P Threonine Thr T Amino Acids Nomenclature  Amino Acid Substituents four substituents: – a carboxyl group – an amino group – a hydrogen atom – an R group (a side chain unique to each amino acid) glycine has a second hydrogen atom instead of an R group  The Amino Acid Residues in Proteins are L Stereoisomers two possible stereoisomers = enantiomers optically active D, L system specifies absolute configuration  Amino Acids Share Many Features, Differing Only at the R Substituent Capacity to polymerize Useful acid-base properties Structure, Size, Water Electric charge, solubility  Amino Acids Can Be Classified by R Group five main classes according to their polarity or tendency to interact with water at biological pH: – nonpolar, aliphatic (7) – aromatic (3) – polar, uncharged (5) – positively charged (3) – negatively charged (2) Amino Acids Classification Nonpolar, aliphatic R groups the hydrophobic effect stabilizes protein structure (G) (A) (P) (V) I has a chiral carbon in its side chain (L) (I) (M) Aromatic R Groups can contribute to the hydrophobic effect R groups absorb UV light at 270–280 nm (F) (Y) (W) Polar, Uncharged R Groups R groups can form hydrogen bonds T has a chiral carbon in its side chain (S) (T) (C) cysteine can form disulfide bonds (N) (Q) Cysteine can form disulfide bonds Positively Charged R Groups have significant positive charge at pH 7.0 imidazole guanidinium (K) (R) (H) Negatively Charged R Groups have a net negative charge at pH 7.0 (D) (E) Uncommon Amino Acids Found in Proteins Reversible Modifications of Amino Acids Selenocysteine: The 21st aminoacid (Sec, U) Incorporated during protein translation. Coded by UGA Lovanov AV et al. Crit Rev Biochem Mol Biol. 2010 Aug;45(4):257-65. doi: 10.3109/10409231003786094. Not all amino acids are constituents of proteins 2. Acid-base properties  Amino Acids Can Act as Acids or Bases amino groups, carboxyl groups, and ionizable R groups = weak acids and bases Low pH pH = pI High pH “amphoteric” or “ampholytes”  Titration of Amino Acids cation ⇌ zwitterion ⇌ anion —COOH has an acidic pKa (pK1) —NH3+ has a basic pKa (pK2) the pH at which the net electric charge is zero is the isoelectric point (pI) Information from a Titration Curve quantitative measure of the pKa of each ionizing group regions of buffering power relationship between its net charge and the pH of the solution – isoelectric point, pI  Amino Acids as Buffers buffers prevent changes in pH close to the pKa glycine has two buffer regions: – centered around the pKa of the ±-carboxyl group (pK1 = 2.34) – centered around the pKa of the ±-amino group (pK2 = 9.6) buffer regions  Isoelectric Point, pI for amino acids without ionizable side chains, the isoelectric point (pI) is: pK1 + pK 2 pI = 2 pH = pI = net charge is zero (amino acid least soluble in water, does not migrate in electric field) pH > pI = net negative change pH < pI = net positive charge Titration of Amino Acids with an Ionizable R Group pK1 + ppK KR2 pKR1 ++ pK 2 pK pI = pI = 2 2 Titration of Amino Acids with an Ionizable R Group pK1 + ppK KR2 pKR1 ++ pK 2 pK pI = pI = 2 2 Effect of the Chemical Environment on pKa ±-carboxyl group is more acidic than in carboxylic acids ±-amino group is less basic than in amines 3. Peptides and proteins Proteins are polymers of amino acids In proteins, amino acids are joined in characteristic linear sequences through a common amide linkage, the peptide bond. The amino acid sequence of a protein constitutes its primary structure.  Peptides Are Chains of Amino Acids peptide bond: – covalent – formed through condensation – broken through hydrolysis residues Peptide Types by the Number dipeptide = 2 amino acids, 1 peptide bond tripeptide = 3 amino acids, 2 peptide bonds oligopeptide = a few amino acids polypeptide = many amino acids, molecular weight < 10 kDa protein = thousands of amino acids, molecular weight > 10 kDa  Peptide Terminals numbering (and naming) starts from the amino-terminal residue (N-terminal) N-terminal C-terminal serylglycyltyrosylalanylleucine Ser–Gly–Tyr–Ala–Leu SGYAL  Estimating the Number of Amino Acid Residues number of residues = molecular weight/110 average molecular weight of amino acid = ~128 molecule of water removed to form peptide bond = 18 128 – 18 = 110  Peptides Can Be Distinguished by Their Ionization Behavior ionizable groups in peptides: – one free ±-amino group – one free ±- carboxyl group – some R groups Peptides: A variety of Functions Hormones and pheromones – insulin and glucagon (think sugar metabolism) – oxytocin (think childbirth) – sex-peptide (think fruit fly mating) Antioxidant – glutathione Neuropeptides – substance P (pain mediator) Antibiotics – polymyxin B (for Gram – bacteria) – bacitracin (for Gram + bacteria) Protection, e.g., toxins – amanitin (mushrooms) – conotoxin (cone snails) – chlorotoxin (scorpions) How long are polypeptides chains in proteins?  Some Proteins Contain Several Subunits multisubunit protein = 2+ polypeptides associated noncovalently oligomeric protein = at least 2 identical subunits – identical units = protomers Proteins show different amino acid composition  Some Proteins Contain Chemical Groups Other Than Amino Acids conjugated proteins = Table 3-4 Conjugated Proteins Class Prosthetic group Example contain permanently Lipoproteins Lipids ² 1-Lipoprotein of blood associated chemical (Fig. 17-2) components Glycoproteins Carbohydrates Immunoglobulin G (Fig. 5-20) – non–amino acid part Phosphoproteins Phosphate groups Glycogen phosphorylase (Fig. 6-39) = prosthetic group Hemoproteins Heme (iron porphyrin) Hemoglobin (Figs 5-8 to 5-11) lipoproteins contain lipids Flavoproteins Flavin nucleotides Succinate dehydrogenase (Fig. 19-9) Metallproteins Iron Ferritin (Box 16-1) Zinc Alcohol dehrogenase glycoproteins contain (Fig. 14-12) sugars Calcium Calmodulin (Fig. 12-17) Molybdenum Dinitrogenase (Fig. 22-3) Copper Complex IV (Fig. 19-12) metalloproteins contain specific metals 4. Characteristics of the peptide bond  Protein Structure Nobel Prize in Chemistry 1954 The Nobel Peace Prize 1962 The Peptide Bond Is Shorter Than a Single Bond Resonance or Partial Sharing of Two Pairs of e- The peptide bond has partial double-bond character Partial negative charge and partial positive charge sets up a small electric dipole Most of the peptide bonds are Trans Most of the peptide bonds are Trans: R groups in opposite sides Cis-Pro bounds  Peptide C—N Bonds Cannot Rotate Freely 6 atoms of the peptide group lie in a single plane partial double-bond character of C—N peptide bond prevents rotation, limiting range of conformations  Dihedral Angles Define Peptide Conformations 2 dihedral angles: – Æ(phi) = between −180 and +180 degrees – È (psi) = between −180 and +180 degrees – É (omega) = œ180 degrees for trans http://bioinformatics.org/molvis/phipsi/  Prohibited Conformations many Æ(phi) and È (psi) values are prohibited by steric interference – Æand È cannot both = 0 degrees http://bioinformatics.org/molvis/phipsi/ Ramachandran Plot Characteristics of the Peptide Bond Partial double-bond character It is Rigid and Planar Trans Configuration It is a Dipole