Lecture 2 - Macromolecules of Life Proteins Nucleic acids...

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Unformatted text preview: Macromolecules* of Life Proteins Nucleic acids Carbohydrates Lipids * Large molecules that are made of up subunits are called macromolecules 28 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: Amino group Carboxyl group R group = side chain composed of one or more atoms ²  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) Polar Hydrophilic (water loving) Acidic Basic 30 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 •  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) Polypeptide chain Amino acids joined by peptide bonds N-terminus C-terminus Peptidebonded backbone Amino group Carboxyl group Side chains 32 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 Protein folding •  Primary (linear AA) sequences are folded into: – Secondary, – Ter3ary and – Quaternary structures •  Structure follows sequence •  Func<on follows structure 34 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 Normal red blood cells Single change in amino acid sequence 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 The two most important configura<ons of proteins that allow H-­‐binding are Alpha helices and Beta sheets 36 α-­‐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 “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 α-­‐helix” Linus Pauling Winner of Noble prize in Chemistry and Peace 37 β-­‐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 38 Ter<ary Structure 39 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) 40 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 ß-­‐sheets Protein folding 42 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 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 44 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 •  Pathogenic form serves as template that recruits normal proteins into misfolding CJD 45 What do proteins do? •  An9body –  An<bodies are part of the immune system. They bind to specific foreign par<cles, such as viruses and bacteria •  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 •  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 •  Transport/storage –  These proteins bind and carry atoms and small molecules within cells and throughout the body 46 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 Free energy Transition state Ea with enzyme Reactants Ea ΔG does not change ΔG Progress of reaction Products 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 Enzyme Transition state Products Shape changes 1. Initiation: Reactants bind to 2. Transition state facilitation: 3. Termination: Products have the active site in a specific orientation, forming an enzyme-substrate complex Interactions between enzyme and substrate lower the activation energy required. lower affinity for active site and are released. Enzyme is unchanged after the reaction. 48 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 4.  Allosteric Regula<on –  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 Allosteric regulation Substrates Enzyme or Enzyme in absence of regula<on or Shape changes Regulatory molecule Allosteric activation or Shape changes Regulatory molecule Allosteric deactivation Regulatory molecule 49 See video on class website 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 ...
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This note was uploaded on 02/14/2012 for the course BIOL 200 taught by Professor Jimlara/stevehauska/hannalerhoula-baker during the Winter '09 term at University of Washington.

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