Chem 1152: Ch. 19 Proteins

Structures of Amino Acids Proteins and polypeptides are biochemical compounds consisting of amino acids – Chains of amino acids bonded together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues Proteins – Longer and more complex than polypeptides – Typically folded into a globular or fibrous form – Structure facilitates a biological function Amino acid Polypeptide Peptide linkages Protein

Amino Acids Organic compounds with amino and carboxylate functional groups Each AA has unique side chain (R) attached to alpha (α) carbon Crystalline solids with high MP’s Highly-soluble in water Exist as dipolar, charged zwitterions (ionic form) Exist as either L- or D- enantiomers Almost without exception, biological organisms use only the L enantiomer Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011; Berg JM, Tymoczko JL, Stryer L, Biochemistry, 5 th Edition, 2002

Amino Acids From McKee and McKee, Biochemistry, 5th Edition, © 2011 by Oxford University Press

Amino Acids  Amino Acid Classes  Classified by their ability to interact with water  Nonpolar amino acids contain hydrocarbon groups with no charge  Figure 5.2 The Standard Amino Acids From McKee and McKee, Biochemistry, 5th Edition, © 2011 by Oxford University Press

Amino Acids  Amino Acid Classes Continued  Polar amino acids have functional groups that can easily interact with water through hydrogen bonding  Contain a hydroxyl group (serine, threonine, and tyrosine) or amide group (asparagine)  Figure 5.2 The Standard Amino Acids From McKee and McKee, Biochemistry, 5th Edition, © 2011 by Oxford University Press

Amino Acids  Amino Acid Classes Continued  Acidic amino acids have side chains with a carboxylate group that ionizes at physiological pH  Basic amino acids bear a positive charge at physiological pH  At physiological pH, lysine is its conjugate acid (-NH 3 + ), arginine is permanently protonated, and histidine is a weak base, because it is only partly ionized  Figure 5.2 The Standard Amino Acids From McKee and McKee, Biochemistry, 5th Edition, © 2011 by Oxford University Press

Formation of Polypeptides Polypeptides and proteins are created through formation of peptide bonds between amino acids – Condensation reaction Polypeptide Peptide linkages

Some Important Peptides Vasopressin – Reduces the volume of urine formed in the body to retain water Oxytocin – Causes contractions in smooth muscles of uterus Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

Proteins have different levels of structure Primary (1°): Sequence of amino acids – Determines 3D structure Secondary (2°): H-bonding interactions between AA residues begin to produce regular, identifiable structures – Alpha (α) helices – Beta (β) strands – Random coil Tertiary (3°): Overall structure of single protein in 3 dimensions Quaternary (4°): Assemblies of multiple polypeptides and/or proteins

Proteins 1° Structure: The Sequence of Amino Acids Primary (1°): Sequence of amino acids – Primary structure held together by peptide bonds – Protein sequence determined by sequence of a gene in the genetic code – Determines 3D structure

Protein Secondary Structure Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

Proteins 2° Structure: The α-helix Backbone N-H groups form H-bonds with C=O group four residues away in sequence AA’s in an α helix arranged in a right-handed helix Each amino acid residue is rotated 100° relative to previous residue in helix – Helix has 3.6 residues per turn

Proteins 2° Structure: The β-sheet Beta (β) sheets formed by H-bond connected strands β strands are elongated helices without helical H-bonds β Sheets may be parallel or antiparallel

Proteins 2° Structure: Random Coils and Loops Proteins typically contain regions lacking either sheet or helical structures. These regions may be classified as: – Random Coils – Loops Loops may perform important structural and functional roles, including: – Connecting β strands form antiparallel sheets – Increasing flexibility (hinge motion) – Binding metal ions or other biomolecules to alter protein function

Proteins 3° Structure Protein function determined by 3D shape Tertiary structure results from residue interactions: – H-bonding – Disulfide Bridges – Salt Bridges – Hydrophobic Interactions Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

Proteins 3° Structure Polar and charged residues tend to be on surface of protein, exposed to water, while hydrophobic residues tend to be buried Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

Proteins 4° Structure Functional proteins may contain two or more polypeptide chains held together by the same forces that control 3° structure: – H-bonding – Disulfide Bridges – Salt Bridges – Hydrophobic Interactions Each chain is a subunit of structure Each subunit has its own 1°, 2° and 3° structure Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

Proteins are Large Macromolecules Proteins are extremely large – MW of glucose is 180 u, compared with 65,000 u for hemoglobin Proteins synthesized inside cells remain inside cells – The presence of intracellular proteins in blood or urine can be used to test for certain diseases Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

Protein Functions Catalytic Function: – Enzymes are proteins that catalyze biological functions Structural function: – Most human structural materials (excluding bone) are comprised of proteins – Collagen (bundled helices) 25-35% of total protein in body Tendons ligaments Skin Cornea Cartilage Bone blood vessels gut – Keratin (bundled helices) Chief constituent of hair, skin, fingernails

Protein Functions Storage Function: – Storage of small molecules or ions – Ovalbumin Main protein in egg whites Can be broken down into amino acids for use by developing embryos – Ferritin Globular complex of 24 protein subunits Buffers iron concentration in cells Ovalbumin (chicken egg white) ferritin

Protein Functions Protective Function: – Protection against external foreign substances Antibodies – Very large proteins – Combine with, and destroy viruses, bacteria Harris, L. J., Larson, S. B., Hasel, K. W., Day, J., Greenwood, A., McPherson, A. Nature 1992, 360, ; Immunoglobulin – blood clotting/Coagulation thrombin – Protease responsible for platelet aggregation and formation of fibrin

Protein Functions Regulatory Function: – Protein hormones Insulin – Protein hormone that directs cells in the liver, muscle, and fat to take up glucose from the blood and store it as glycogen – Forms hexamer bound together by Zn Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Insulin

Protein Functions Nerve impulse transmission: – Rhodopsin Protein found in rods cells of eye retina – Converts light events into nerve impulses sent to the brain

Protein Functions Movement function: – Proteins involved in muscle contraction Myosin Actin

Protein Functions Transport function: – Transport ions or molecules throughout the body Serum albumin: Transports fatty acids between fat and other tissues Hemoglobin: Transports O 2 from lungs to other tissues (e.g., muscles) Transferrin: Transports iron in blood plasma ; Serum albuminhemoglobin transferrin

Protein Classifications Fibrous Proteins – Comprised of long stringlike molecules that can wrap around each other to form fibers – Usually insoluble in water – Major components of connective tissues (e.g., collagen, keratin) Globular proteins – Spherical – Usually water soluble – May be moved through the body (e.g., hemoglobin, transferrin) Based on structural shape Based on composition Simple Proteins – Contain only amino acid residues Conjugated Proteins – Contain amino acid residues and other organic or inorganic components (i.e., prosthetic groups) Lipoproteins Glycoproteins metalloproteins