Amino Acids & Proteins

Amino Acids & Proteins Central Dogma: process by which the instructions in DNA are converted into a functional product, proposed by Watson and Crick (DNA → RNA → Protein) Reverse Transcription: takes RNA and converted it to complementary DNA (cDNA), typically via the protein reverse transcriptase (normally used in retroviruses: have an RNA genome, turns RNA → DNA and integrates the DNA into the host’s genome) RNA Viruses: have genetic information stored as RNA and can be used by host’s machinery to make proteins straight from it as if it were mRNA or have copy its RNA template in order to use that copy for protein synthesis (i.e. SARS, flu, measles) ncRNA: non-coding RNAs are RNA molecules that are not used for translation but are instead directly used for functions within the cell (i.e. tRNA and rRNA) Epigenetics: study of heritable changes in gene expression that do not involve underlying changes to DNA sequence (change in phenotype without a change in genotype); affects how the cell reads its genes and explains how all cells have the same DNA but are expressed very differently Can be done through DNA methylation (typically acts to repress gene expression) and histone modification (addition of acetyl groups is known to increase expression of genes) Amino Acid Structure: amino group (N-terminus), carboxylic acid group (C-terminus), alpha carbon is connected to the R group; formed by a dehydration/condensation reaction (amide bond between two amino acids - a carbonyl groups next to it) The peptide bond (between amino and carbonyl) exhibit a lot of resonance and have double bond character (meaning this bond is pretty rigid and planar) The peptide bond is broken through a hydrolysis reaction (think of hydrating the molecule in order to split it up) Acid Hydrolysis: basically add heat and acid, its very non-specific and will split up any peptide bond Proteolysis: breaks specific bonds using a protease (i.e. Trypsin: cuts at C terminal of Arg & Lys) Histidine: side chain with a pKa of 6.5 (close to physiological pH), important because histidine can exist in protonated or deprotonated forms and can be important in an enzyme's active site Proline: its side chain wraps around and connects with the N-atom in the backbone (gives it a secondary alpha amino group - since it’s bound to 2 carbons as opposed to 1) Glycine: simplest of all amino acids, one H atom; no chiral alpha-carbon (all the other amino acids have a chiral residue); also very flexible Alpha Helix Breakers: glycine and proline (glycine is so flexible that it doesn’t hold it steady and proline introduces kinks into the structure) Proline is typically seen as the first residue of an alpha helix because of its stability Cysteine: special thiol group (-SH group); can form disulfide bridges between nearby cysteine side chains (oxidation); bridge can be broken through a reduction reaction (intracellular → reducing environment | extracellular → oxidizing environment) Cysteine vs. Cystine: the first is in its reduced form and the latter is in its oxidized form Fischer Projection: help to highlight the Epimer relationship of the four groups around a chiral carbon L-aa and D-aa’s are enantiomers of one another (also the horizontal lines come out of the plane, towards us while the vertical ones go into the plane, away from us) L-aa means amino groups is on the left of the alpha carbon and the D-aa means the amino group is on the right of the Alpha-carbon Amino acids found within the human body will be the L configuration ONLY Isoelectric Point: point along a pH scale at which a molecule exists in a neutral form with 0 charge (iso=equal) Must know the pKa’s of the amino group and the carboxylic acid groups Equation: !"# 1 % !"# 2 2 = 𝑝𝐼 (On average, amino pKa is about 9 and carboxylic acid is about 2) Zwitterion: when a molecule has both a negative and a positive charge present Nonpolar Amino Acids (Hydrophobic): Alkyl Side Chains: glycine (not technically alkyl), alanine, valine, methionine, leucine, isoleucine, and proline Aromatic Side Chains: phenylalanine and tryptophan Polar Amino Acids (Hydrophilic): Neutral Side Chains: serine, threonine, asparagine, glutamine, cysteine, and tyrosine Acidic Side Chains: aspartic acid (aspartate) and glutamic acid (glutamate) Basic Side Chains: histidine, lysine, arginine Primary Structure: linear sequence of amino acids Secondary Structure: the way that the linear sequence folds upon itself and is determined by backbone H-bond interactions (alpha helices and parallel/antiparallel beta sheets) Tertiary Structure: higher order of folding within a polypeptide chain, is dependent on distant group interactions; stabilized by H bonds, Van der waals interactions, hydrophobic packing (hydrophobic residues hide on the interior of the protein), and disulfide bridge formation (single polypeptide) Quaternary Structure: the bonding/interactions between multiple polypeptides (subunits); stabilized by the same things as tertiary structure Conformation: folded 3D structure of a protein (ACTIVE) Denatured: unfolded structure of a protein (INACTIVE); can be done through temperature change, pH, chemicals, and enzymes Temp: destroys secondary, tertiary, and quaternary structure of a protein pH: destroys the tertiary and quaternary structure (breaks ionic bonds) Chemical: disrupts H-bond interactions (secondary, tertiary, and quaternary structure) Enzymes: disrupts primary, secondary, tertiary, and quaternary structure because it breaks apart the peptide bonds within the protein Solvation Shell: layer of solvent that is surrounding the protein