BIOL 302 Lecture 3 Outline of Last Lecture I. Chemical ReactionA. Laws of ThermodynamicsB. Enzymatic CatalysisC. Prosthetic groups, coenzymes and co-factorsII. Regulation of Enzyme ActivityA. Feedback inhibition & Allosteric regulationB. Enzyme inhibitorsIII. Free energy of moleculesA. Activated carrier moleculesB. HydrolysisOutline of Current Lecture I. General Protein functionA. Amino acidsB. Hydrophobic interactionsII. Protein StructureA.Denaturation, prion diseasesB.Folding patternsC.Levels of organizationIII. Feedback InhibitionA. Allosteric proteinsB. PhosphorylationC. Nucleotide hydrolysisD. Affinity chromatographyCurrent LectureCh 4: Protein Structure and FunctionProteins are the most structurally complex & functionally sophisticated molecules. “Functional unit” within the cell.- General protein functions:- Structure: provides cell with shape and structure (tubulin and actin)- Enzymes: catalyze covalent bond breakage or formation (pepsin)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Transport protein: carries other molecules/ions (hemoglobin-oxygen)- Motor: movement in cells and tissues (myosin)- Storage: store small molecules or ions (ferritin-iron in liver)- Signal: carries signals from cell to cell (insulin-glucose levels)- Receptor: detects signals and transmits them to cell’s response machinery (insulin receptor)- Gene regulatory protein: binds to DNA to switch genes on/off (transcriptional factors-lactose repair)Amino acids- building blocks (monomers) that form proteins.- 20 different amino acids, each with varying chemical properties (acidic, basic, hydrophobic, hydrophilic)- Protein is made from a chain of amino acids, each amino acid is linked to its neighboring amino acid through covalent bonding (peptide bond).- Amino acids contain a central alpha carbon, an amino group (N terminus), a carboxyl group (C terminus), and an R- group (side chain)- N and C termini allow for directionality of amino acids, considered to be the backbone ofpeptide. Also provide polarity to polypeptide chain.- Peptide bonds are formed b/w backbone of protein. NOT b/w R groups.- Amino acid links are formed through condensation reactions (water molecule is expelled)- Linkages of aa’s through covalent peptide bonds creates long, flexible molecules that canfold in on themselves, creating specific conformations. When polypeptide chains fold in on themselves, noncovalent interactions constrain it in various ways. It takes numerous noncovalent interactions to hold polypeptide in tight conformation, they can form b/w polypeptide backbone or other R groups.- Hydrophobic interactions help proteins fold into small, compact conformations. Hydrophobic=water-fearing. The hydrophobic side chains of an amino acid fold in an arrangement that allows them to interact with other hydrophobic side chains, and stay awayfrom the aqueous environment surrounding them leaving the hydrophilic (water-loving) sidechains to face the outside of the protein and interact with the aqueous environment. - Each protein folds into a single, stable conformation. Hydrogen bonds within a protein molecule can help stabilize that conformation. Even though hydrogen bonding is a fairly weak bond, multiple hydrogen bonds can add to the structural integrity of the molecule, aiding in its stabilization.- Proteins are considered to be most functional when folded in their proper conformation. However, proteins can also be “unfolded”, or denatured, by solvents/factors that disrupt the noncovalent interactions holding them in their stable confirmation. Examples of factors that can denature proteins: exposure to high heat, exposure to acidic or alkaline reagents (varies depending on the protein), urea, etc.- If the factor that denatures the protein is removed, the protein can re-fold (renature) itself back to its stable conformation - Incorrectly folded proteins can develop into protein aggregates and damage cells or tissues. Prion diseases (mad-cow disease, CJD) are caused from misfolded protein aggregates. This occurs through a rare conformational change where the protein folds abnormally. The abnormally folded protein is called a PrP (Prion Protein), and can form heterodimers (dimer=two proteins bound to one another) with the “normal” form of the protein.- The “normal” form of the protein gets converted into the abnormal PrP form, causing a homodimer. This process continues until you have an aggregate of abnormal proteins being formed.Proteins are very diverse, structurally and functionally, and come in a variety of shapes/sizes in orderto facilitate their specific role(s) within the cell/tissues. - Proteins can range in size from 30 amino acids to 10,000 amino acids in length. They can be globular, fibrous, forming filaments, sheets, rings, or spheres. - Proteins exhibit common folding patterns, with the α-helix and β-sheet being the most common - The alpha helix folding pattern (or motif) is demonstrated in a linear sequence of amino acids that folds in a helical (ex-spiral staircase) manner that is stabilized internally through hydrogen bonds between the polypeptide backbone (The N-H bonding in the amino terminus of every peptide bond is hydrogen-bonded to the C=O of a neighboring peptide bond located four amino acids away in the same chain) - The β-sheet folding pattern involves neighboring regions of the polypeptide chain that are associated side-by-side through hydrogen bonding, and give it a flat/rigid structure. The individual strands in the sheet are held together by hydrogen-bonding between peptide bonds in different strands, and side chains in each strand project alternately above and below the plane of the sheet - Proteins can span the lipid bilayer of cell membranes (transmembrane proteins). If the polypeptide chain contains hydrophobic amino acids, the hydrophobic side chains orient themselves outward so that they can interact with the hydrophobic fatty acid tails of the lipid bilayer. - Alpha helices can also interact and intertwine with each other. When they do this, it is referred to as a “coiled-coil” interaction. The helices do this coiled-coil arrangement in order to minimize the exposure of their hydrophobic residues to their surrounding aqueous environment - Beta sheets can be found in 2 varieties: parallel or