Chapter 3 – Protein - Structure and FunctionMost abundant BIOMOLECULE in the cell. C, H, O, NMonomer = Amino acid-Most proteins are composed of only 20 different amino acids.-All amino acids have: A central carbon with four bonds, attachedto these four components:1. A basic amino group, NH3+2. An acidic carboxyl group, COO-3. A hydrogen atom4. An R-group, also called a side chain (only variable among the 20 aminoacids)1. The nature of side chains:-The side chain makes each of the 20 amino acids unique.-Side chains can have functional groups that affect reactivity-Polarity affects solubility. Polar side chains are hydrophilic, and nonpolarside chains are hydrophobic-Side chains containing carboxyl, sulfhydryl, hydroxyl, or amino groups tend to be both soluble and reactiveQuestion: The three amino acids shown in the diagram are hydrophilic? Hydrophobic? Polar?2. How do amino acids link to form proteins?-Polymerization is the process of linking monomers (subunits) to form a polymer (a long chain of subunits)-A protein is a polymer that consists of linked amino acid monomers-Polymerization always requires an input of energy-The peptide bond: A peptide bond is the C-N bond between the carboxyl group of one amino acid and the amino group of the next amino acid. Peptide bonds are unusually stable and help provide a structural framework or “backbone” for the entire molecule. (N-C-C-N-C-C-N-C-C……..)The side chains extend out from the backbone. The backbone has directionality, with a free amino group at one end and a free carboxyl group at the other end. N  C terminal. The backbone is flexible3. Proteins Are the Most Versatile Large Molecules in Cells- Catalysis: proteins called enzymes catalyze chemical reactions-Defense: antibodies and complement proteins attack viruses and bacteria-Movement: motor proteins can move things within cells and are responsible for muscle movement-Signaling: peptide hormones and receptor proteins facilitate cell-cell communication-Structure: proteins in cell membranes and in the extracellular matrix give cells and tissues a specific shape-Transport: cell membrane proteins move substances across the plasma membrane into and out of cells4. What Do Proteins Look Like? Protein structure-Proteins differ in size, shape, and the chemistry of the amino acids-A protein’s structure has four basic levels of organization(i) Primary structure is the amino acid sequenceEvery protein has a unique sequence of amino acids –Sequence of amino acids (peptide bonded)The sequence of amino acids dictates all higher levels of protein structure due to the nature of the R-groups present. N  CEven small changes in the amino acid sequence can result in significant changes in overall protein function. Example: hemoglobin and sickle-cell anemia1(ii) Secondary structure emerges when parts of the polypeptide backbone interact-Each peptide bond is polar because the amino group has a slight positive charge and the carboxyl group has a slight negative charge-The carboxyl portion of one peptide bond can form a hydrogen bond with the amino portion of anotherpeptide bond-The hydrogen bonding (among backbone atoms) can result in two different structures: α-helix, β-pleated sheet. Which one forms, if either, is determined by the primary structure (peptide bonding)(iii) Tertiary structure is due to side-chain interactions-The secondary structure brings R-groups in close proximity to one another-Depending on their identity, R-groups can interact in the followingways:-Hydrogen bonds can stabilize interactions between two polar R-groups-Hydrophobic interactions cause hydrophobic side chains to coalesceinto a globular mass-Van der Waals interactions stabilize hydrophobic side chains oncethey are near each other-Covalent bonds called disulfide bridges can occur between the sulfur-containing R-groups of two cysteine residues-Ionic bonds can form between oppositely charged R-groups(iv) Quaternary structure arises when different polypeptides interact (not present in all proteins)-Many proteins are actually multiplepolypeptide chains (subunits) foldedtogether-The subunits are held together by thesame interactions between R-groups thatstabilize tertiary structure. Thedifference is that the interactions arebetween R-groups on separatepolypeptide chains  dimers, trimers,tetramers etc….5. Folding and functionWhat do proteins look like?  Fibrousand Globular proteins?Most elements of protein structure (and function) are based on folding of polypeptide chains Folding happens spontaneously because the folded molecule is more stable energetically than the unfolded molecule. Leucine is a hydrophobic amino acid. In a folded membrane protein, where would you expect to find Leucine? Folding is essential for normal function. example: protein enzymes “active site”Folding in the cell is often facilitated by molecular chaperones 6. Enzymes: An Introduction to Catalysis Enzymes lower activation energy -Spontaneous reactions have an overall decrease in free energy but need an investment of energy (activation energy) to get going-Activation energy is the energy necessary to reach the transition state.2*Reactions happen only when reactants can reach the transition state, an intermediate state of new and old bonds. Reactants can reach the transition state on their own if they have enough kinetic energy.*The kinetic energy of molecules is a function of their temperature; therefore, reactions proceed faster athigher temperatures-Enzymes are catalysts, meaning that they lower activation energy*A catalyst is not consumed in the reaction and does not affect the overall energy change (∆G).*Proteins that catalyze reactions are called enzymes  Biological Catalysts.Most of the important reactions in the cell would proceed at very slow rates, or not at all, without enzymes.-How do enzymes work?*Enzymes have an active site where reactants (substrates) bind*The active site is usually a cleft or cavity on a globular enzymeHow do enzymes and substrates interact to catalyze a reaction?-An enzyme binds specifically to a particular reactant or set of reactants (lock-and-key model)-Enzymes often flex or change shape when they bind to a substrate (a flexible “lock”). This change in shape is called induced fit-After the binding, interactions with R-groups at the active site stabilize the transition stateEnzyme catalysis is a three-step process:1. Initiation: the enzyme precisely orients