Amino Acids, Peptides and Proteins Chapter 3 Part 1 1 CHAPTER 3, Part 1 Amino Acids and Peptides Learning goals: • To know the structure and naming of all 20 protein amino acids • To know the structure and properties of peptides and the particularly the structure of the peptide bond. • Ionization behavior of amino acids and peptides at different pH’s. • To know the general pKa’s of amino acids: their carboxyls, aminos, the R-group weak acids. 2 Proteins: Enzymes, Binding Proteins, Structural Proteins – all made from Amino Acids 3 Amino Acids: Building Blocks of Protein • Proteins are linear heteropolymers of -amino acids • Amino acids have properties that are well-suited to carry out a variety of biological functions – – – – Capacity to polymerize Useful acid-base properties Varied physical properties Varied chemical functionality 4 Amino acids share many features, differing only at the R substituent 5 L and D forms 6 Carbon Numbering System A 7 Amino Acids: Classification Common amino acids can be placed in five basic groups depending on their R substituents: • Nonpolar, aliphatic (7) • Aromatic (3) • Polar, uncharged (5) • Positively charged (3) • Negatively charged (2) 8 Invented the One Letter Amino Acid Code. 9 10 11 12 13 14 Spectrophotometry 15 UV light Absorption by Proteins – due to 2 Amino Acids 16 Cysteine can form Disulfide Bonds 17 Uncommon Amino Acids 18 Amino acids in Proteins Can be Reversibly Modified A 19 Non Protein Amino Acids 20 Toxic Amino Acids A search for compounds producing Yunnan Sudden Unexplained Deaths found related to eating a mushroom. Halford, B. C+E News Feb 13, 2012 Trogia venenata Zhu 21L Which Form Occurs in Water ? 22 Glycine Acid/Base Titration 23 Compare Amino Acids to Simple Carboxylic Acids and Amines 24 Glutamate has 3 pKa’s 25 Histidine has 3 pKa’s 26 How to Calculate the pI When the Side Chain is Ionizable • Identify species that carries a net zero charge • Identify pKa value that defines the acid strength of this zwitterion: (pK2) • Identify pKa value that defines the base strength of this zwitterion: (pK1) • Take the average of these two pKa values What is the pI of histidine? 27 Peptide Bond Formation Where does this occur? Where does this occur? 28 Structure of a Simple Peptide Ser-Gly-Tyr-Ala-Leu or SGYAL 29 Naming peptides: start at the N-terminus • Using full amino acid names – Serylglycyltyrosylalanylleucine • Using the three-letter code abbreviation – Ser-Gly-Tyr-Ala-Leu • For longer peptides (like proteins) the oneletter code can be used – SGYAL 30 AEGK 31 Aspartame A 32 Peptides: A Variety of Functions • Hormones and pheromones – insulin (think sugar) – oxytocin (think childbirth) – sex-peptide (think fruit fly mating) • Neuropeptides – substance P (pain mediator) • Antibiotics – polymyxin B (for Gram – bacteria) – bacitracin (for Gram + bacteria) • Protection, e.g., toxins – amanitin (mushrooms) – conotoxin (cone snails) – chlorotoxin (scorpions) 33 Proteins are: • Polypeptides (covalently linked -amino acids) + possibly: • cofactors • coenzymes • functional non-amino acid component metal ions or organic molecules organic cofactors NAD+ in lactate dehydrogenase prosthetic groups covalently attached cofactors heme in myoglobin • other modifications 34 35 36 37 Sample Written Exercise - Choose One 1. You have a solution of tyrosine. You decided to modify Y by methylation of the carboxyl, explain how this would change the acid-base titration of this molecule. 2. You have a solution of tyrosine. You decided to modify Y by methylation of the “alcohol”, explain how this would change the acid-base titration of this molecule. 3. You have an 28 amino acid long peptide that contains three cysteines. Explain why when examining the structure of this peptide the same two cysteines were involved in a disulfide bond, but not the other one. 38 Things to Know and Do Before Class 1. Know Structure and chemistry of all 20 amino acids. 2. Approximate pKa of amino acid ionizable groups and their ionization state at different pH’s. 3. Modifications of amino acids in proteins. 4. Disulfide bonds, make and break them, and diagram them. 5. The Peptide bond, make and break it, and diagram them. 6. EOC Problems 1, 2, 3a, 4-7: we will have problems to solve (clicker questions) in class like these. Please practice these well before class. 39