Lecture02_4Jan12_28-50_6ppg - Macromolecules of Life Amino...

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Unformatted text preview: 12/31/11 Macromolecules* of Life Amino Acids & Proteins Amino acids, thought to be formed in the prebio<c soup, are the building blocks of proteins 20 major forms, with a common structure: Proteins Nucleic acids Carbohydrates Lipids * Large molecules that are made of up subunits are called macromolecules 28 Amino group Carboxyl group R group = side chain composed of one or more atoms The size and shape of the R group determines unique features, including interac<ons and reac<vity with other molecules 29 Interac<ons of Amino Acids with Water Side chains: Nonpolar Hydrophobic (water ha<ng) Polymeriza<on of Amino Acids The building blocks of proteins (amino acids) and other subunit-containing macromolecules are referred to as monomers They are polymerized into polymers 10mer, 50mer, k-mer Polar Hydrophilic (water loving) Acidic Basic 30 The bond formed between amino acids is called a pep3de bond A chain of amino acids is called a polypep3de Also referred to as a pep3de if short (~<50 AA) Polymeriza3on requires energy and is nonspontaneous 31 Polypep<de forma<on (Condensation reaction) What proper<es dis<nguish the 20 Amino Acids? 1 The loca<on of the carbonyl group 2 The loca<on of the amino group 3 The composi<on of the side chains or R groups 4 The ability to form pep<de bonds 33 Polypeptide chain N-terminus Amino acids joined by peptide bonds C-terminus Peptidebonded backbone Carboxyl group Side chains Amino group 32 1 12/31/11 Protein folding Primary (linear AA) sequences are folded into: Secondary, Ter3ary and Quaternary structures Primary Structure The amino acid sequence of the protein Essen<ally limitless possibili<es 1020 or ~100 million trillion possible 10-mers Has profound effects on the eventual structure and func<on of the protein, cell and organism Normal amino acid sequence of hemoglobin Single change in amino acid sequence Structure follows sequence Func<on follows structure Normal red blood cells 34 Sickled red blood cells 35 Secondary Structure Sec<ons of proteins are shaped largely due to H-bonding between carbonyl-O and amino-H in the backbones of different amino acids -Helix 1 2 3 4 5 Determined by AA composi<on & sequence Characterized by H-bonds along the chain Almost co-axial with planar amide groups About 3.6 residues per turn of the helix Side chains are projected outward The two most important configura<ons of proteins that allow H-binding are Alpha helices and Beta sheets 36 "I took a sheet of paper and sketched the atoms with the bonds between them and then folded the paper to bend one bond at the right angle, what I thought it should be rela9ve to the other, and kept doing this, making a helix, un9l I could form hydrogen bonds between one turn of the helix and the next turn of the helix, and it only took a few hours of doing that to discover the -helix" Linus Pauling Winner of Noble prize in Chemistry and Peace 37 -Sheet 1 Characterized by hydrogen bonds crossing between chains 2 Strands are not fully extended due to side chain steric interference 3 The AA chain is slightly "puckered" so that the beta sheet is some<mes said to be "beta pleated sheet" 4 H-bonding chains may run parallel (both chains running N- terminal to C-terminal in the same direc<on) or an<parallel Ter<ary Structure 38 39 2 12/31/11 Quaternary Structure Combina<ons of dis<nct polypep<des interac<ng to form a single structure Dimers Protein formed from two of the same polypep<des Heterodimers Protein formed from two different polypep<des Trimer, tetramer.... (mul<mer) The structural proper3es of proteins are traceable back to: 1. van der Waals forces 2. Their quaternary structure 3. The amino acid sequence 4. Hydrogen bonding between amino acids within -sheets 40 Protein folding Protein unfolding (denatura<on) Usually results in loss of func<on Egg whites, normally transparent and liquid, are irreversibly denatured with heat, resul<ng in a white, interconnected, solid mass Denatura<on can be reversible e.g., Ribonuclease In this example, a disulfide reducing agent is added to break the disulfide bonds linking two Cysteines Reversible denatura<on can also be accomplished with heat or high salt concentra<ons 42 43 Folding (and intracellular transport) is olen facilitated by molecular chaperones Chaperonins Undergo large conforma<onal changes (requires ATP) that allow the chaperonin to bind an unfolded or misfolded protein, encapsulate that protein within one of its cavi<es, and release the protein back into solu<on Extreme Consequence of Misfolding PrP - Normal Cell Protein Pathogenic Prion Protein Prions (proteinaceous infec<ous par<cles) cause fatal spongiform ecephalopathies: scrapie in sheep, mad cow disease, and Kuru and Creutzfeld-Jacob disease in humans 44 Pathogenic form serves as template that recruits normal proteins into misfolding CJD 45 3 12/31/11 What do proteins do? An9body Enzyme Enzymes carry out almost all of the thousands of chemical reac<ons that take place in cells. They also assist with the forma<on of new molecules by reading the gene<c informa<on stored in DNA Enzymes = Proteins ac<ng as Catalysts Most chemical reac<ons in cells don't occur fast enough to support life unless a catalyst is present Catalysts lower the ac<va<on energy (Ea) and increase the reac<on rate Enzymes bring reactants together in the correct orienta<on and stabilize transi<on state molecules An<bodies are part of the immune system. They bind to specific foreign par<cles, such as viruses and bacteria Transition state Free energy Messenger Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, <ssues, and organs Structural component These proteins provide structure and support for cells. On a larger scale, they also allow the body to move Reactants Ea G does not change G Ea with enzyme Products Transport/storage These proteins bind and carry atoms and small molecules within cells and throughout the body 46 Progress of reaction 47 Enzyme Regula<on Enzymes are flexible and dynamic 1. "Induced fit" Structural change following substrate binding Results in <ghter binding to "ac<ve site" of enzyme Substrates Transition state Products 2. Chemical Modifica<on e.g., phosphoryla<on, cleavage, glycosyla<on 3. Compe<<ve Inhibi<on The substrates cannot bind when a regulatory molecule binds to the enzyme's ac<ve site The ac<ve site become available (ac<va<on) or unavailable (deac<va<on) to the substrate when a regulatory molecule binds to a different site on the enzyme Competitive inhibition Substrates Enzyme or or Shape Regulatory changes molecule or Shape Regulatory changes molecule 4. Allosteric Regula<on Allosteric regulation Enzyme Shape changes 1. Initiation: Reactants bind to the active site in a specific orientation, forming an enzyme-substrate complex 2. Transition state facilitation: Interactions between enzyme and substrate lower the activation energy required. 3. Termination: Products have lower affinity for active site and are released. Enzyme is unchanged after the reaction. Enzyme in absence of regula<on 48 Allosteric activation Allosteric deactivation Regulatory molecule See video on class website 49 Which property does an enzyme NOT have? 1 Changes the free energy of a reac<on 2 Changes the ac<va<on energy of a reac<on 3 Precisely orients reactants in space 4 Controlled by allosteric regula<on or compe<<ve inhibi<on 50 4 ...
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This note was uploaded on 03/08/2012 for the course BIOL 180 taught by Professor Freeman during the Fall '07 term at University of Washington.

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