1. Amino Acids and Proteins
Protein Structure and Function: An Overview
Proteins are polymers of amino acids, connected by dipeptide bonds. Amino acids play central roles both as building blocks of proteins and as intermediates in metabolism. There are 20 common amino acids found in proteins, and depending on their sequencing, and the overall protein structure (which we learn about in our second protein lecture), they convey an vast array of chemical properties.

2. What We Will be Learning
Amino acid and Protein Structure and Function:
Types of Amino Acids and properties
Acid Base Properties of Amino Acids, zwitterions & isoelectric points
Molecular Handedness and Amino Acids, identifying enatiomers
Peptide bonding
Mechanism and properties for higher levels of protein organization

3. Amino Acid Structure
Amino acid refers to the presence of two specific functional groups:
An amine group
A carboxylic acid
The terminology “amino acid” stems from the presence of two specific functional groups. The amino group and a carboxylic acid group. These two functional groups are bound covalently to a central atom. If you follow the link on this slide you will an animation of amino acid bonding, and be able to look at the variety of side chains found in amino acids.

4. DiPeptide bond
When the carbonyl carbon atom loses an oxygen atom, and the second amino acid contributes two hydrogen atoms, a dipeptide bond forms joining the two amino acids.
When two amino acids join, a dipeptide forms. The carbonyl carbon atom of the first amino acid bonds directly to the nitrogen atom of the second amino acid as shown here:

5. Polypeptide Chains Ser-Leu-Thr-Ser-Val.
A chain of amino acids that contains more than about 5 amino acids is called a polypeptide.
There will be practice in naming polypeptide chains provided in mastering chemistry
Ser-Leu-Thr-Ser-Val.

6. Variations of Amino Acids
This central carbon is bound to 4 distinct groups
While each amino acid has an amine group and a carboxylic acid, there is variation in the side chain
The smallest amino acid is glycine – with two hydrogen atoms attached (in addition to the amine group and carboxylic acid). All other amino acids contain an alpha carbon with four different groups bound thus they are each chiral atoms.
Glycine
variation in the side chain

7. The R Group polar and neutral, acidic and polar, basic and polar.
There are four different classes of amino acids determined by different side chains (R group):
non-polar and neutral,
polar and neutral,
acidic and polar,
basic and polar.
R groups are acidic, basic or neutral. Neutral groups are either polar or nonpolar. The dipolar ion in which the amino and carboxylic acid groups are both ionized is known as a zwitterion. Each amino acid has an isoelectric point—the pH at which the numbers of (+) and (-) charges in a sample are equal.

8. Non Polar Amino Acids
Aliphatic side chains of hydrocarbon give non polar amino acids
Even though the Sulfur is electronegative, the length of the chain makes methionine non polar and hydrophobic

9. Identifying Side Chains
Follow the link to the Johnkyrk site. Move through the tutorial until you see the slide that looks like the image above. Select the appropriate “buttons” to examine the acidic, basic, non polar and uncharged side chains

10. Non polar Amino Acids with Aromatic Rings
Phenylalanine
Tyrosine
Tryptophane
Like the amino acids with aliphatic hydrocarbon based R groups – phenylalanine, Tyrosine, and Tryptophane are non polar and hyrdrophobic.

11. Polar Amino Acid R groups that give polar amino acids: Amides Hydroxyl
Sulfur in a short chain

12. Amino Acids with Charged Side chains
Acidic R groups contain a carboxylic acid functional group
Basic R groups contain an amino functional group (not amide- these are not polar enough to ionize).
The amino functional group will act as a proton acceptor – a base. The amide functional group has the double bond to oxygen, delocalizing the charge and preventing it from acting as a base. R groups with a carboxyl group donate a proton – acting as an acid. These side chains result in amino acids that are charged and hydrophilic.

13. Acid Base Properties of Amino Acids
The carboxyl group of an amino acid can lose a hydrogen ion
R-COOH <——> R-COO– + H+
The amine group can accept a hydrogen ion
R-NH3+ <——> R-NH2 + H+
Transfer of the H from the –COOH group to the –NH2 group forms a neutral dipolar ion, an ion that has one (+) charge and one (-) charge.

14. Neutral dipolar ions are known as zwitterions.
Amino acids share many of the properties we expect from salts:
can form crystals
have high melting points
are soluble in water
not soluble in hydrocarbon solvents

15. Ionization state of the Zwitterions depends on pH
At neutral pH, amino acids in solution exist as dipolar ions
It is usual to write the formula for an amino acid indicating the Zwitterion state – with a positive charge at the amine group, and a negative charge at the carboxyl group
The amino group is protonated -NH3+
carboxyl group is deprotonated (-COO-)

16. At high pH – basic conditions, both groups become deprotonate
In acidic solution (low pH), amino acid zwitterions accept protons on their basic –COO- groups to leave only the positively charged –NH3+ groups.
As the pH increases, the carboxyl group will lose the proton, and both groups will be charged
At high pH – basic conditions, both groups become deprotonate
As the pH increases, the carboxyl group will lose the proton, and both groups will be charged
At high pH – basic conditions, both groups become deprotonate

17. Isoelectric point
The pH at which the net positive and negative charges are evenly balanced
Each amino acid has at least two pKa values (the pH at which the weak acid and its conjugate base are present in equal amounts), one for the alpha carboxyl group and one for the alpha amino group

18. PKa– 9.7
The carboxyl group pKa value for all amino acids fall around “2” and the amino group pKa values fall around “9-10”.
Pka 1= 2.4
PKa2 – 9.7
Pka = 2.4

19. Handedness Chiral: Having right- or left-handedness
non superimposable mirror images
Achiral:
superimposable mirror images and thus no right- or left handedness
You can not move the “hand” to cover the image of the hand – it is non superimposable, however, you can imagine sliding the chair over the image of the chair – these two images are achiral – lacking in “handiness”

20. Handiness in Molecules
Like the mirror image of the hand – these molecules can not be superimposed – they have “handiness”
If a molecule has an atom bonded to four different groups, it is chiral

21. Alanine is Chiral
The mirror-image forms of a chiral molecule like alanine are called enantiomers or optical isomers.

22. R & S Nomenclature
Identify the group with the lowest priority (low atomic number as #4 – highest priority as #1
Draw an arrow from low number to high number
If the arrow traces a clockwise movement, the enantiomer is the R enantiomer.
If it is counterclockwise, it is the S enantiomer.

23. Archiral – lacking in handiness
Propane is an achiral molecule. The molecule and its mirror image are identical and it has no left- and right-handed isomers

24. Amino Acids are Chiral Only glycine is achiral
The naturally occurring amino acids are classified as left-handed or L-amino acids
In nature, only one enantiomer of most chiral biological compounds, such as amino acids is present.
As a result, different enantiomers of a compound may have substantially different biological effects.

25. Enantiomers
Enantiomers of a compounds have the same formula and atomic connections but different spatial arrangements.
The same physical properties except they always differ in their effect on polarized light
They differ in how they react with other chiral molecules.
Pairs of enantiomers often differ in their biological activity, odors, tastes, or activity as drugs.

26. Amino Acids are Chiral
Spearmint leaves and caraway seeds have very different flavors - imparted by a pair of enantiomers
Pairs of Enantiomers often differ in their biological activity, odors, tastes, or activity as drugs.

27. Levels of Protein Structure
Primary protein structure: The sequence in which amino acids are linked by peptide bonds in a protein.
We have been focused today on the primary protein structure – we are going to briefly introduce the higher levels of organization today – but return to look at them in depth next week.

28. Convention in Writing Peptide Chains
peptides are always written with the N-terminal on the left, and the carboxyl terminal on the right
Individual amino acids joined in the chain are referred to as residues

29. Proteins have four levels of structure
Primary structure is the sequence of amino acids in a protein chain
Secondary structure is the regular and repeating spatial organization of neighboring segments of single protein chains
Tertiary structure is the overall shape of a protein molecule produced by regions of secondary structure combined with the overall bending and folding of the protein chain.
Quaternary structure refers to the overall structure of proteins composed of more than one polypeptide chain

30. Intermolecular forces determine the shapes and functions of proteins
The non-polar hydrophobic side chains are pushed and pulled into clusters within a large protein molecule
Hydrophilic groups on the surface of folded proteins impart water solubility to the proteins.
Myoglobin has hydrophobic amino acid R groups packed into the interior , while those on the surface are hydrophilic – making the molecule water soluble
Link

31. Intermolecular Forces In Proteins

32. Secondary Protein Structure
The secondary structure includes two kinds of repeating patterns known as the a-helix and the b-sheet.
In both, hydrogen bonding between backbone atoms holds the polypeptide chain in place.

33. Alpha-helix Secondary Structure
The stabilizing hydrogen bonds of the alpha helix point to the C-terminus and are nearly parallel to the long axis of the spiral of the helix.

34. Beta-sheet secondary structure.
The protein chains usually lie side by side.
the R groups point above and below the sheets
The protein chains usually lie side by side.
the R groups point above and below the sheets

35. Tertiary Protein Structure
The three-dimensional shape that results from the folding of a protein chain is the protein’s tertiary structure.
Depends on interactions of amino acid side chains that are far apart along the same backbone.

36. Quaternary Protein Structure
The way in which two or more polypeptide subunits associate to form a single three-dimensional protein unit.

37. Protein Structure in Review

38. Quaternary structure
This is found in proteins that have multiple polypeptide subunits.
Noncovalent interactions:
hydrophobic interactions :
interactions between nonpolar R groups on different subunits
hydrophilic interactions (electrostatic)
interactions between polar R groups on different subunits
salt bridges (electrostatic)
Interactions between acidic R group and basic R group on different subunits
generally buried in the interior of a protein
Covalent interactions:
disulfide bridges between two cysteine residues that have been oxidized
(form after protein has folded to further stabilize structure)

39. What is it all For?

40. Goals Recaped Recognize an amino acid and describe the basic structure
illustrate how amino acids link together to form peptide chains and proteins.
Use the structure and size of side chains to predict polarity and charge in acid and basic conditions
Understand amino acids as zwiterions and the concept of isoelectric point.

41. Be able to identify chiral molecules and chiral carbon atoms
Be able to identify enatiomers
Draw and name a simple protein structure from the amino acid sequence
The importance and meaning of disulfide bonds, hydrogen bonds, and non covalent interactions in determining secondary, tertiary and higher levels of protein structure
Be able to describe protein hydrolysis and denaturation, and give some examples of agents that cause denaturation.