Proteins Dinosaur Protein
Proteins - classified by functions Enzymes Transport Proteins Storage Proteins Contractile (Motor) Structural (Support) Defensive (Protect) Receptors (detect stimuli) Regulatory (Signal)
Protein Structure • Proteins are unbranched polymers • Monomers are Amino Acids • Standard Amino Acids (20/700) Classified according to side-chain polarity • Non-Polar • Polar Neutral • Polar Acidic • W/ 2nd carboxyl group • Polar Basic • W/ 2nd amine group • Essential vs.Non-essential • PVT. TIM HALL
Amino acids central carbon = the -Carbon Covalently bonded to the alpha carbon is: 1) a Hydrogen atom, H 2) a carboxyl functional group, (COOH) 3) an amine functional group, (NH2) 4) a side chain (R). Each side chain distinguishes one kind of amino acid from another.
Protein Chirality Most a-amino acids in living creatures are Levo-oriented, not Dextro-oriented (opposite of chirality in monosaccharides) “Handedness” (L or D) in standard amino acids: Line up the C chain vertically and look at the position of the horizontally aligned -NH2 group.
Acid-Base Properties • Amino Acids can participate in “internal” acid-base reactions. There is an internal donation of a H+ ion from the COOH group to the NH2 group. The result is a double ion, both positive and negative, whose charges cancel each other out. Isolated amino acids (neutral solution) are zwitterions
Equilibrium of Amino Acids • Depending on the pH of the solution the equilibrium position is “pushed” in a particular direction. • Remember to consider the source of extra ions!
Isoelectric Points & Electrophoresis • Isoelectric point: the pH at which the amino acid has no net charge (zwitterion) • This point is measured in an electric field • The movement of charged molecules in an electric field is the basis for electrophoresis.
Peptide Bonds • Peptide bonds = covalent bonds between the carboxyl group on one amino acid and the amino group on an adjacent amino acid • This is a Condensation Reaction • A polypetide chain has an “N” terminal and a “C” terminal
Biochemically Important Small Peptides • Hormones • Ex.: Oxytocin, Vasopressin • Both have 9 amino acids • Neurotransmitters • Ex.: Enkaphalins • Morphine & Codeine bind to the same sites • Antioxidants • Ex.: Glutathione
Protein Structure • Proteins have at least 50 amino acids • Monomeric vs. Multimeric • Simple vs.Conjugated 4 levels of protein structure: primary -linear sequence of a.a.'s (held together by peptide bonds) secondary - arrangement in space of the backbone portion (caused by hydrogen bonds between carbonyl oxygen and amino hydrogen at different locations on the chain) tertiary - complete 3-D shape of a peptide (caused by hydrogen bonds, disulfide bonds, electrostatic attractions & hydrophobic attractions quaternary - spatial relationships between different polypeptides or subunits
Primary (1o) structure: the amino acid sequence Like letters forming words: Same letters used over, but sequence changes. Misplaced letters may still be readable. Missing letters may ruin the “word” Human myoglobin.
Results of changing the Primary sequence: • Polymorphism: proteins vary in primary sequence but have the same function. • Between species [different a.a. sequences] • Within a species [liver vs. kidney] • Site Specificity: unique sequences determine intra-cellular location of transmembrane signals, binding sites, etc… • Families of Proteins: different but related functions evolved from a single ancestral protein e.g. trypsin, chymotrypsin, and elastase (protein choppers) • Homologous Proteins: structurally similar; may perform the same cellular function, but in different species • e.g.: cytochrome-C • in duck & chickens = 2 variants • in yeast & horses = 48 variants • Mutation - change in primary amino acid sequence = a defective protein • e.g. sickle cell
Secondary structure : • Highly patterned sub-structures: • helix or • pleated sheet or • unstructured “random” chain segments. • Spatial arrangement of protein backbone. • There can be many different secondary structures • present in one single protein molecule
Secondary Structure The hydrogen bonding between the carbonyl oxygen atom of one peptide linkage and the amide hydrogen atom of another peptide linkage.
Helix • H-bonds between every 4th amino acid • Most are right-handed spirals • R-groups point outward & toward N-terminal Extensible structure – springy!
4 views of the a helix protein structure: (a) Arrangement of protein backbone. (b) Backbone with hydrogen-bonding shown. (c) Backbone atomic detail shown. R groups point away from the long axis of the helix
pleated sheet • Two types: parallel and anti-parallel • R-groups point outward on sides • NOT extensible – NOT springy • Short segments (5-8 residues) that fold & H-bond into ZIG-ZAG pleated sheets. • Localized shapes. • Resist pulling (tensile) forces = strengthof silk
pleated sheet protein structure: (a) emphasizing the H bonds (---) between chains. (b) emphasizing pleats and location of R groups.