AminoAcids 11

BIOC 460 Summer 2011

Amino Acid Structures and Chemical

Properties 1

Introduction to Proteins;

Amino Acids, the Building Blocks

of Proteins

Reading: Berg, Tymoczko & Stryer: Chapter 2, pp. 25-34

Appendix to Chapter 2, pp. 60-61 (visualizing protein structures)

Review General Chemistry notes for acid-base concepts (it will be assumed you understand the material).

A very useful website for studying amino acids structures and properties:

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

Key Concepts

• 4 levels of protein structure:

1. Primary (1°)

2. Secondary (2°)

3. Tertiary (3°)

4. Quaternary (4°)

• Properties of the 20 amino acids that occur in peptides and proteins are crucial to the structure and function of proteins

– Stereochemistry

– Relative hydrophobicity or polarity

– Hydrogen bonding properties

– Ionization properties

– Other chemical properties




Properties 2

Protein Structure -- Overview

• Primary structure: linear sequence of amino acids

– polymer of amino acid residues (~50-1000)

– linked by peptide bonds (covalent, amide linkages)

• Terminology: amino acid residue, polypeptide (chain)

• Building blocks: 20 amino acids (different side chains)

• Protein function depends on correct 3-D folding of polypeptide

– 3-D folded structure determined by AA sequence

– Most proteins’ functions involve binding other molecules

• Shape complementarity (steric, van der Waals interactions)

• Chemical complementarity (hydrogen bond donors/acceptors, charge complementarity, etc.)

• Often the hydrophobic effect is important in binding.

• Flexibility in structure (proteins are not rocks!)

Structure of lactoferrin changes when it binds iron

(common phenomenon, induced fit)

Berg et al., Fig. 2-3

ribbon diagram, just “backbone”

atoms of polypeptide chain

(easier to trace chain from one end

to the other)

Space-filling structure, all

atoms of polypeptide chain



Properties 3

Biological Roles of Proteins (examples)

1. Catalysis (enzymes)

2. Transport (e.g., hemoglobin - O2 transport in blood;

transport of ions across cell membranes)

3. Storage (e.g., myoglobin - oxygen storage in muscle; seed

proteins - storage of nutrients)

4. Coordinated motion (e.g., in muscle, cilia, flagella)

5. Mechanical support (e.g., collagen)

6. Protection (e.g., immune system - antibodies; blood

clotting proteins)

7. Regulation and communication (e.g., hormones,

receptors, gene activation and repression, control of

enzyme activity)

8. Generation and transmission of nerve impulses

9. Toxins (bacterial, plant, snake, insect)

Levels of Protein Structure 1. Primary structure (1° structure):

– Defined sequence of AAs

– linked by peptide bonds (amide linkages)

2. Secondary structure (2° structure): – local, regular/recognizable conformations observed

for parts of peptide backbone of a protein

– e.g, α-helix, β conformation, collagen helix

3. Tertiary structure (3° structure): – 3-dimensional conformation of whole folded

polypeptide chain

4. Quaternary structure (4° structure): – 3-dimensional relationship of different polypeptide

chains (subunits) – how the subunits fit together and their symmetry

relationships – only in proteins with more than 1 polypeptide chain



Properties 4

Levels of Protein Structure

Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig. 3-16

a-Amino Acids

• carboxylic acids, so “a", “b" “g", etc. designate order of additional C atoms on carboxyl group.

a carbon = central C atom, with 4 different substituents:

1. a-carboxyl group

2. a-amino group

3. hydrogen atom

4. R group = “side chain” (different structures for 20 different amino acids)

• Stereochemistry: D vs. L

a carbon chiral (4 different substituents)

– Enantiomers (non-superimposable complete mirror images)

– All AAs in naturally occurring proteins are L-isomers.

R



Properties 5

a-Amino Acids, Stereochemistry

Berg et al.,

Fig. 3-4

UA’s BMB Biology Project

website on amino acids

As you "travel" ONward,

from carbonyl C toward

N of amino group,

in L-amino acids

R group is on left.

Are there naturally-

occurring D-amino

acids?

a-Amino Acids, Ionization

a-carboxyl group a-amino group

Berg et al., Fig. 2-6



Properties 6

a-COOH group: a weak acid

•can DONATE its proton

•pKa ~ 2-3

What's the conjugate base form of the carboxyl group?

Which form is charged?

Is it a positive or a negative charge?

a-NH2 group: a weak base

•unshared pair of electrons on the :N

•neutral amino group can ACCEPT a proton.

•pKa ~9-10

What's the conjugate acid form of the amino group?

Which form is charged?

Is it a positive or a negative charge?

pKas of a-amino and a-carboxyl groups are different for

different amino acids, and also are altered if they're the

terminal groups on chain of AAs, i.e., a peptide or protein.

Amino Acid Ionization, continued

• Besides the a-carboxyl and a -amino groups, 7 of the 20

AAs have ionizable side chains.

Structures and Properties of AA side chains

Biology Project website on amino acids, highly recommended

for studying: http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

Categories of AA side chains (ONE way to classify them)

• Aliphatic side chains

• Aromatic side chains

• Hydroxyl-containing side chains

• Sulfur-containing side chains

• Basic side chains

• Acidic side chains

• Amide side chains




Properties 7

Amino Acids with Aliphatic Side Chains (nonpolar)

Which of the 20 amino acids is achiral

(has no asymmetric C)?

Which aliphatic AA has 2 chiral centers?

Amino Acids with Aromatic Side Chains

Which of the aromatic side chains would be the least polar

(the most hydrophobic)?

Do any of the aromatic side chains have an ionizable group

(the ability to dissociate a proton)? Which? Approx. pKa?



Properties 8

Amino Acids with Hydroxyl-Containing Side Chains

Does either of the hydroxyl-containing amino acids have

2 chiral centers? Which?

Amino Acids with Sulfur-Containing Side Chains

Which of the two S-containing side chains would be

more hydrophobic?



Properties 9

Amino Acids with “Basic” Side Chains

(Structures are those that predominate at pH 7)

Why is the His side chain (imidazole group) called “basic”

if the predominant form at pH 7 is unprotonated?

Amino Acids with Acidic Side Chains and their Amides

(Structures are those that predominate at pH 7)

Are the amide side chains of glutamine and asparagine

ionizable, i.e. can they gain or lose a proton? Why or why

not?



Properties 10

Proton Dissociation Reactions of Amino Acids with

Ionizable Groups in Proteins

Berg et al., Table 2-1

[imidazole group]

[side chain

carboxyls]

Proton Dissociation Reactions of Amino Acids with

Ionizable Groups in Proteins

Berg et al., Table 2-1

[thiol group]

[aromatic

hydroxyl group]

[-amino group]

[guanidino

group]



Properties 11

Titration of an amino acid with a non-ionizable R group (Gly)

Nelson & Cox,

Lehninger Principles

of Biochemistry,

4th ed., Fig. 3-10

Titration of an amino acid with an ionizable R group (His)

Nelson & Cox,

Lehninger Principles

of Biochemistry,

4th ed., Fig. 3-12b



Properties 12

Classification of AA side chains by chemical properties

• Nonpolar but rather H2O-soluble (not hydrophobic):

Gly, Pro

• Nonpolar, hydrophobic

Ala, Val, Leu, Ile, Met, Phe, (Trp), (Cys)

• Polar, uncharged at pH 7:

Amide-containing:

Asn, Gln

Hydroxyl-containing:

aliphatic OH: Ser, Thr

aromatic OH: Tyr

• Aromatic:

Phe, Tyr, Trp



Properties 13

Classification of AA side chains by chemical properties

• Charged (at pH 6-7), polar:

Acidic (–):

Asp (carboxyl), Glu (carboxyl)

Basic (+):

Lys (ε-amino), Arg (guanidino), (His) (imidazole)

• Ionizable but predominantly uncharged at pH 7:

Cys (thiol), Tyr (phenolic OH)

• Sulfur-containing:

Cys (thiol), Met (thioether)

Learning Objectives

• Explain the 4 levels of protein structure: primary, secondary, tertiary, and quaternary.

• Draw the structure of a typical amino acid, indicating the following features: α-carbon, α-carboxyl group, α-amino group, sidechain (“R group”), and ionic forms that predominate at acidic (say, pH 1), neutral (pH 7), and basic (pH 13) pH values.

• Classify each of the 20 common amino acids found in proteins according to side chain type (aliphatic, aromatic, sulfur-containing, aliphatic hydroxyl, basic, acidic, amide, hydrophilic (polar), hydrophobic (nonpolar). (These categories overlap extensively, e.g., glutamate is acidic and it’s very polar.)

• Learn the general structure of each of these 20 amino acids, with its full name and 3-letter abbreviation. DO THIS NOW – DON’T PUT IT OFF. You will not have to know how many C’s are in a side chain, but you should be able to recognize them.



Properties 14

Learning Objectives, continued

• Be able to write the ionization (protonation/deprotonation) reactions for the 9 ionizable functional groups (7 side chains plus terminal α-amino and α-carboxyl groups); determine the charge of each form (conjugate acid and conjugate base) for each group.

• Be very familiar with the approximate (“typical”) pKa values of theses ionizable groups (R groups, α-amino,and α-carboxyl groups) in peptides and proteins (not the free amino acid).

• Note: numerical values of these "generic " pKa values for the ionizable functional groups in peptides and proteins will be on the cover sheet of Exam 1.

• For a given ionizable group, given its pKa and pH, be able to determine the charge on that group.

AminoAcids 11

Documents

structure proteins

quaternary structure

secondary structure

tertiary structure

proteins amino acids

amino acid structures

amino acids structures

d folded structure