BMS 531.02 Amino Acids and Proteins PDF

Amino Acids and Proteins Introduction BMS 531.02 SPRING 2025  Objectives 1. Compare and contrast the chemical and structural features of amino acids and describe how these features contribute to behavior with particular emphasis on functional groups 2. Explain the role of side...

Amino Acids and Proteins Introduction BMS 531.02 SPRING 2025  Objectives 1. Compare and contrast the chemical and structural features of amino acids and describe how these features contribute to behavior with particular emphasis on functional groups 2. Explain the role of side chains in amino acids and how they contribute to the chemical and functional behavior of amino acids 3. Summarize the generation of peptide bonds and explain the process from the perspective of the functional groups involved 4. Evaluate protein structure by doing the following: ◦ List and describe the levels of protein structure and the importance of amino acid structure to protein structure ◦ Explain how each level of structure is defined and influenced by the lower level structures ◦ Compare and contrast denaturation and renaturation/folding ◦ Describe examples where altered folding affects protein function with an impact on human health 5. Explain how proteins are classified and list the types/categories of proteins based on the classification system 6. Determine and describe the changes in behavior of amino acids as changes in environmental conditions (i.e. pH) occur (Henderson-Hasselbalch) – This will be revisited during the learning activity after the second week of classes ◦ Calculate pH, pKa, and pI values ◦ Calculate changes in pH and pKa LO1, LO2, LO3 AMINO ACIDS Proteins are generated from “building blocks” of Amino Acids Amino acids are linked by peptide bonds Functional groups define protein activity and are located as side chains of the amino acids 20 amino acids ◦ 5 Electrically-charged; Hydrophillic; forms IONIC bonds ◦ 5 Polar; Hydrophillic; form HYDROGEN bonds ◦ 3 SPECIAL; due to unusual characteristics ◦ 7 Non-Polar; Hydrophobic; cluster or associated within hydrophobic regions  LO1, LO2, LO3 Basic Structure and Stereochemistry General Amino Acid: AMPHOTERIC: ◦ Both basic and acidic Stereoisomers/enantiomers (except Glycine) ◦ Optically active isomers due to ability to rotate plane-polarized light ◦ D (right) and L (left) ◦ ALL amino acids incorporated into proteins = L ◦ This matters because enzymes and environments in the body are CHIRAL in nature; they can distinguish forms and select only L forms Adapted From: Baynes and Dominiczak. Medical Biochemistry (2018) LO4, LO5 Proteins in general… Diverse in shape, size, and function ◦Enzymes = proteins that catalyze reactions (lysozyme) ◦Defensive Proteins (antibodies) ◦Hormones (insulin) ◦Receptors (both on and in cells) (acetylcholine receptor) ◦Transport proteins (hemoglobin) ◦Structural (collagen) ◦Genetic Regulatory Proteins (transcription factors) LO4 Callback to BMS532: Yay! Review! Protein Structure Primary (1°) = sequence of amino acids Secondary (2°) = patterns in different regions of a polypeptide chain; dependent on primary structure ◦ Α-helix ◦ Β pleated sheet Tertiary (3°) = folding of the polypeptide chain; dependent on both primary and secondary structure Quaternary (4°) = interaction of two or more polypeptide chains  Amino Acid Structure and the LO1, LO2, LO3, LO4 Relationship with Protein Structure Consider Proline Imino acid: Proline ◦ Cannot keep side chain as far away from other side chains; causes a kink/bend in polypeptide structure LO4 Protein Folding: 2° and 3° Protein folding is critical to function Relies on hydrogen bonding and non-covalent interactions Structure of amino acid side chains determines what folding is possible DENATURATION ◦ The loss of 2° or 3° structure ◦ High temps can break the bonds and interactions important in protein folding ◦ pH changes affect ionization of carboxyl and amino groups Misfolded or unfolded proteins can have detrimental consequences (i.e. failure to achieve 4° structures)  Importance of Primary Structure to LO4 Function Primary Secondary Quaternary Red Blood Cell and Tertiary Function Structure Structure Shape Structures 1 Val Normal Normal Proteins do not associate; Normal red 2 His β subunit hemoglobin each carries oxygen. blood cells are full of 3 Leu β individual Normal 4 Thr hemoglobin 5 Pro α proteins. 6 Glu 7 Glu 5 µm β α 1 Val Sickle-cell Sickle-cell Hydrophobic interactions Fibers of β subunit hemoglobin between proteins abnormal 2 His lead to aggregation; hemoglobin Sickle-cell 3 Leu oxygen deform red β 4 Thr carrying blood cell 5 Pro α capacity into sickle 6 Val reduced. shape. 7 Glu 5 µm β α © 2016 PEARSON EDUCATION, INC. LO4 Protein Folding and Thermodynamics Denaturation is relatively simple and often IRREVERSIBLE. Renaturation, if even possible, is complex and difficult. u Normal protein Denatured protein ur MODIFIED FROM PEARSON © 2016 PEARSON EDUCATION, INC. LO5 Types of Proteins: Context and Future Directions Proteins can be classified based on structure, composition, and function ◦ These combined generate protein ‘type’ Classification based on composition is subdivided into 3 categories: simple, conjugated, and derived Classification based on structure relies heavily on 3D appearance and X-ray crystallography Classification based on ‘type’ generates 7 categories of proteins: 1) antibodies, 2) contractile proteins, 3) enzymes, 4) hormonal proteins, 5) structural proteins, 6) storage proteins, and 7) transport proteins ◦ Each of these will make an appearance in the course to varying degrees with enzymes making the first appearance  LO4, LO6 A Bit More About Amino Acids: Polarity and Ionization Actual pKa values vary by several pH units depending on temp, buffer, ligand binding and neighboring functional groups Terminal and side chain groups also differ in pKa Adapted From: Baynes and Dominiczak. Medical Biochemistry (2018)  Alanine Example: LO4, LO6 Introduction to an Application of Henderson-Hasselbalch Amino acids because of their combination of amino groups and carboxyl groups behave differently at different pHs Under physiological conditions: Can act as biological buffers ◦ Range of pH with maximum buffering capacities at the 2 extremes ◦ Acidic form reacts with added base ◦ Basic form reacts with added acid In water: behavior can be as a dipolar ion (zwitterion) ◦ partially protonated middle = isoelectric point (pI) = minimal buffering capacity; extent of protonation varies with pH and the pKa of side chains ◦ Glycine: Acidic Neutral Basic Protonated Protonated Unprotonated Titration in NAOH Amino and Amino only Amino and Carboxyl Carboxyl Adapted From: Baynes and Dominiczak. Medical Biochemistry (2018)