2 nd lec. Amino acids and proteins (2).pptx

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1. Protein Structure and Function Amino Acids

2. Amino Acids and Proteins Proteins are the most abundant and functionally divers molecules in living systems. Every life process depends on this class of molecules.

3. Overview Although, proteins are the most abundant and functionally diverse, yet all share the common structural feature of being linear polymers of amino acids. Examples: Enzymes and polypeptide hormones  direct and regulate metabolism Contractile proteins  movement Collagen + calcium phosphate crystals  bone Hemoglobin and plasma albumin in blood  shuttle molecules Immunoglobulins  fight infectious agents

4. Structure of the amino acids Amino acids are organic molecules possessing both carboxyl and amino groups. There are more than 300 a.a . found in the nature, only 20 standard or common a.a are found in mammalian proteins and these are coded for by DNA The nature of the side chain decides the role of an amino acids in a protein

5. All a.a . (except proline ) has: Carboxylic acid group Primary amino group Hydrogen atom Side chain R group which is distinctive for each amino acid All bounded to the  -carbon atom Primary Structure - Amino Acids

6. Biochemistry 3070 – Amino Acids & Proteins 7 Proline is the only secondary (2°) amino acid or (“ imino ” acid.) Amino acid Proline differs from the other 19 amino acids because: It has secondary amino group. The three carbon side chain is bounded to the amino a group creating a cyclic molecule. Its unique geometry contributes to formation of fibrous structure of collagen

7. Biochemistry 3070 – Amino Acids & Proteins 9 Acidic and basic properties of amino acids The majority of a.a . has amphoteric character , they can act as either an acid or a base –COOH  acidity and –NH 2  basic properties. Carboxylic acids donates a proton in aqueous solution. The pKa for carboxylic acids is normally around 2 to 5. The strength of weak acids is expressed by pK a ( the negative log of the acid dissociation constant) Strong acids have low pKa values and weak acids have high pK values. That is, the pH at which these acids are 50% ionized: R-COO H  R-COO - + H + pH= [less than 2]  [above 5]

8. Biochemistry 3070 – Amino Acids & Proteins 10 Acidic and basic properties of amino acids Amino groups function as bases, accepting a proton. The pKa for amino groups is usually around 9 – 10. Again, at the pKa these groups are 50% ionized: R-N H 3 +  R-NH 2 + H + pH= [below 8]  [above 9]

9. Biochemistry 3070 – Amino Acids & Proteins 11 Even though both acids and amines are present in the same molecule, they mostly behave as though they were separate entities:

10. Biochemistry 3070 – Amino Acids & Proteins 12 Summary: At low pH, proton concentration [H+]is high. Therefore, both amines and carboxylic acids are protonated. ( -NH 3 + & -COOH ) At high pH, proton concentration is low. Therefore, both amines and carboxylic acids are deprotonated. ( -NH 2 & -COO - ) At neutral pH, amines are protonated( -NH 3 + ) and carboxylates are deprotonated (-COO - )

11. Biochemistry 3070 – Amino Acids & Proteins 13 “ Zwitter ” Ions: Zwitterions, molecules that have both a positive and a negative charge Ions bearing two charges were named zwitter ions by German scientists; the name still applies today, especially for amino acids at neutral pH: + H 3 N – CH 2 – COO -

12. Biochemistry 3070 – Amino Acids & Proteins 14 Acid-Base Properties of Amino Acids Draw the following chemical structures for glycine : (Non-existent form :) H 2 N – CH 2 - COOH pH=1: + H 3 N – CH 2 - COOH pH=7: + H 3 N – CH 2 – COO - pH=12: H 2 N – CH 2 – COO -

13. Amino acids classification The properties of the amino acid vary as the structure of side chain ( R ) varies. These variations of the side chains greatly influence the overall three dimensional structure, shape, conformation of a protein. Amino acids can be classified according to the properties of their side chains. C C O O – R H H 3 N +

14. Classification of Amino Acids They classified according to the side chain: Amino acids with nonpolar side chains. Aromatic R Groups. Amino acids with uncharged polar side chains. Positively Charged (Basic) R Groups. Amino acids with acidic side chains.

15. A. Amino acids with non-polar side chains R-group does not bind or give off protons or participate in hydrogen or ionic bonds R-groups can be thought of as “oily” or “lipid like”  a property that promotes hydrophobic interactions.

16. Hydrophobic ( nonpolar ) R groups

17. Hydrophobic (nonpolar) R Group

18. Hydrophobic (non polar) R groups Glycine ( Gly,G ) is the smallest amino acid and its R group is simply a hydrogen atom. It is the only one that is achiral . Whereas the side chain of alanine (Ala, A), is a methyl group -CH3 Valine (Val, V) has a three carbon branched side chain Leucine and isoleucine each contain a four carbon branched side chain. Valine , leucine and isoleucine are known as branched chain a.a . and highly hydrophobic

19. Location of non polar amino acids in proteins: proteins found at the aqueous solutions, the side chain of non-polar amino acids tend to cluster together in the interior of the protein. The hydrophobic interaction is important in stabilizing protein structure. However, for proteins that are located in a hydrophobic region such as a membrane, the nonpolar side chain group are found on the out side surface of the protein, interacting with the lipid environment. Alanine , valine , leucine and isoleucine play an important role in establishing and maintaining the 3D structures of proteins because of their tendency to cluster away from water

20. Hydrophobic Amino acids Hydrophilic Amino acids

21. B. Amino acids with uncharged polar side chains These a.a . have zero net charge at neutral pH Side chains of cysteine and tyrosine can lose protons at alkaline pH Serine, threonine , tyrosine each contain a polar hydroxyl groups can participate in H-bonding R-groups of asparagine and glutamine, containing an amide group each, can also participate in H-bonding.

22. Amino acids with uncharged polar side chains: 1. Side chains as sites of attachment for other compounds: Ser, Thr , and rarely Tyr, contain a polar hydroxyl group  as site of attachment for structures e.g., phosphate group. Amide group of Asn , as well as hydroxyl group of Ser or Thr , can be sites of attachment for oligosaccharide chains in glycoproteins

23. Amino acids with uncharged polar side chains: 2. Disulfide bond formation Disulfide bond: the cysteine contains a sulfhydryl ( thiol ) group (-SH), which is an important component of the active site at many enzymes. In proteins –SH groups of two cysteines can become oxidized to form a covalent crosslink called a disulfide bond (-S-S-) The two –SH become oxidized to form a cystine residue, i.e formation of disulfied bond by the oxidation of two cysteine residues producing one cyctine residue.

24. Hydrophilic R Groups with Formal Charge Basic R Groups Acidic R Groups

25. C. Amino acids with acidic side chains Amino acids aspartic and glutamic acid (Asp and Glu resectively ) are proton donors At neutral pH, R-groups fully ionized, containing a negatively charged carboxylate group (–COO - ) Therefore called aspartate and glutamate to emphasize that they are negatively charged at physiologic pH

26. These amino acids have negative charge at neutral pH These amino acids are proton donor at neutral pH

27. C. Amino acids with basic side chains R-groups of basic aa’s accept protons At physiologic pH, R-groups of lysine (Lys) amino group, and arginine ( Arg ) a  guanidine group are fully ionized and positively charged Histidine (His)   imidazole  side chain  is weakly basic, free a.a . is largely uncharged at physiologic pH. When in protein, His R-group can be either positive or neutral depending on the ionic env . provided by the polypeptide chains of the protein. This contributes to role of His in functioning of proteins such as Hb

28. These amino acids have positive charge at neutral pH H + These amino acids are proton acceptor at neutral pH

29. Aromatic R groups a.a . Phenylalanine ( Phe , F): has a hydrophobic benzyl side chain Tyrosine ( Tyr,Y ): a phenol amino acid, has similar structure to Phenylalanine with hydroxyl group added to benzyl side chain. Tryptophan ( Trp , W): contains a bicyclic indole group

30. Amino acid Abbreviated name One-letter symbol Nonpolar R groups: Glycine Alanine Valine Leucine Isolecine Phenylalanine Tryptophan Methionine Proline Gly Ala Val Leu Ile Phe Trp Met Pro G A V L I F W M P Polar, uncharged R: Serine Threonine Tyrosine Cysteine Asparagine Glutamine Ser Thr Tyr Cys Asn Gln S T Y C N Q Acidic R groups: Aspartate Glutamate Asp Glu D E Basic R groups: Lysine Histidine Arginine Lys His Arg K H R

31. Amino Acids You must know: Their names Their structure Their three letter code Their one letter code Tyrosine, Tyr, Y, aromatic, hydroxyl

32. Essential ( indispensable )  Amino Acids is an  amino acid  that cannot be  synthesized  de novo  by the organism, and thus must be supplied in its diet. The nine amino acids humans cannot synthesize are  phenylalanine ,  valine ,  threonine ,  tryptophan ,  methionine ,  leucine ,  isoleucine ,  lysine , and  histidine   Five amino acids are  dispensable  in humans, meaning they can be synthesized in sufficient quantities in the body. These five are  alanine ,  aspartic acid ,  asparagine ,  glutamic acid  and  serine  

33. Biochemistry 3070 – Amino Acids & Proteins 47 Essential Amino Acids: Isoleucine Leucine Lysine Methionine Phenylalanine a Threonine Tryptophan a Valine Arginine b Histidine b a Aromatic b Probably essential

34. Nonstandard amino acids have important function : Not DNA coded Created by modification of standard amino acids that incorporated into polypeptide such as: Histamine synthesized from histidine Tyrosine is metabolized to epinephrine (adrenaline) Tyrosine is also the precursor of the thyroid hormones thyroxine required iodide

35. 1. Enzymes - increase rate of reaction x 1 billion 2. Carriers – hemoglobin, transferrin 3. Receptors – hormones, cytokines 4. Transport – membrane channels 5. Structure – collagen, elastin 6. Protective - immunoglobulins 7. Contractile - muscle, cytoskeleton 8. Regulatory (Hormones)– govern metabolic pathway Types and functions of Proteins

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