Download LS1a Fall 09

LS1a Fall 2014
Section Week #4
I.
Amino acid structure

Proteins are polymers made up of 20 different naturally occurring amino acids.

All naturally occurring amino acids have the same basic structure. They consist of a central carbon
atom – the alpha () carbon atom – connected to three different groups: an amine (or amino)
group, a carboxylic acid group, and a side chain. Different amino acids differ only in having
different side chains; the other components are invariant between the 20 amino acids.
Section Activity #1: Label the side chain, amine group, carboxylic acid group, and -carbon in the
general amino acid structure below.
Side chain
Alpha Carbon
Amine group
Carboxylic acid (“carboxyl”) group
II. Peptide bonds

A peptide bond is an amide bond that connects amino acids to form peptides and proteins.
Section Activity #2: Shown below are alanine and serine in their predominant states at pH 7. Draw
the products of the reaction to form the alanyl-serine dipeptide.

Peptide bonds can be represented by two different resonance forms, as shown below. In real life,
the electron distribution within a peptide bond exists as an average of these two forms.
trigonal planar

One consequence of this resonance is that peptide bonds are highly polar, with oxygen and
nitrogen carrying significant partially negative and positive charges, respectively. This results in an
oxygen that is more partially negative than it normally would be and the amide hydrogen being
more partially positive than it normally would be. This increased polarity contributes to the
strength of the hydrogen bonds that stabilize secondary structure (e.g., -helices and β-sheets).
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Section Activity #3: Answer the following questions about the hexapeptide shown below.
a. Beginning at the N-terminus, write the sequence for this peptide using both the one-letter and
three-letter amino acid codes.
NH2-G-H-V-M-Q-T-COOH
NH2-Gly-His-Val-Met-Gln-Thr-COOH
b. Circle the polar side chains in the structure above.
Histidine, glutamine and threonine are polar.
c.
Draw arrows to identify each peptide bond in the structure above.

Because peptide bonds have partial double-bond character, they are generally not free to rotate;
as a result, the nitrogen adopts a trigonal planar molecular geometry. The double-bond nature of
the peptide bond ensures that the six atoms shown below all lie in the same plane (i.e., are
“coplanar”). The arrangement of groups across double bonds can be either cis or trans, as
shown below.
trigonal planar nitrogen

The alpha ()-carbons of adjacent amino acids are generally positioned trans to each other across
the peptide bond that connects them, but they can also be cis to each other, as shown below.
Trans peptide bonds are heavily favored over cis peptide bonds for all amino acids except for
proline.
Cis configuration

The -carbons of 19 amino acids (all except for glycine) are “chiral” atoms. A chiral molecule is
one whose mirror image is not superimposable on itself (like your left and right hands).

The -carbon of an amino acid is a chiral center for the 19 amino acids in which the -carbon is
bound to four different groups (an amino-group, a carboxyl-group, a side chain, and a hydrogen).
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Glycine is the only amino acid that is not chiral, as its -carbon is bound to two hydrogens in
addition to the amino- and carboxyl-groups.

When describing the chirality of an -carbon, it helps to emphasize the tetrahedral geometry of
the -carbon by using “dashes” (
) and “wedges” (
). Dashes are used instead of a straight
line to indicate a bond that is pointing away from you (or “into the page”). Wedges indicate a
bond that is point towards you (or “out of the page”).

All 19 naturally occurring chiral amino acids (excluding glycine) have the same chirality as shown
in the generic amino acid in section activity #1. If the amino-group is to the left and the carboxylgroup is on the right, the side chain will point out of the page (towards you) if the -carbon is
pointed up. The side chain will point into the page (away from you) if the -carbon is point down.
Section Activity #4:
a. Complete the drawing of the tripeptide below by adding R 3 and H to the third -carbon by
using dashes and wedges to appropriately describe the third amino acid’s stereochemistry.
b. In which molecules is the peptide bond between serine and proline cis? In which molecules is
the peptide bond between proline and alanine cis?
The bonds between serine and
proline are cis in molecules B and
D. The peptide bond between
proline and alanine is cis in
molecule D.
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III.
Amino acids with ionizable side chains

Several amino acids have ionizable side chains.
o
Aspartic acid and glutamic acid have carboxylic acids as their side chains.
o
Arginine, lysine, and histidine are have basic nitrogen atoms in their side chains that can be
protonated.
o
Cysteine has an ionizable thiol (-SH).
o
Tyrosine and serine have ionizable alcohols (-OH).

You need to know the structure of the protonated state that is associated with a particular pK a
value (although you won’t need to memorize pKa values).
Section Activity #5: Sort the 20 amino acids (alanine, arginine, asparagine, aspartic acid, cysteine,
glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine,
proline, serine, threonine, tryptophan, tyrosine, and valine) into the three categories below
(nonpolar, polar, and ionizable).
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Section Activity #6: Two tri-peptides, NH2-E-K-C-COOH and NH2-Y-C-P-COOH, are covalently
attached to each other through their side chains. The pKa values for these amino acids are shown
below.
Amino Acid
pKa
Y
C
K
E
N-terminal Amine
C-terminal Carboxylic Acid
10.0
9.0
11.0
4.0
9.8
2.3
a. Using the full names of the amino acids, write the sequences of both peptides.
Peptide 1: NH2-Glutamic Acid-Lysine-Cysteine-COOH
Peptide 2: NH2-Tyrosine-Cysteine-Proline-COOH
b. Draw the structure of the connected peptides at physiological pH. The NH 2-Y-C-P-COOH
Backbone and one of its side chains are given.
c.
What is the net charge of the connected peptide at physiological pH?
Zero
d. As drawn, is the peptide bond connecting cysteine to proline cis or trans?
Trans
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Section Activity #7: Identify the appropriately drawn amino acid chain(s) and write out its/their
sequence(s) using the three-letter amino acid code and the one-letter amino acid code. If the
tripeptide is drawn incorrectly, identify the errors and correct them.
Correct
NH3+-V-M-G-COONH3+-Val-Met-Gly-COO-
Peptide bonds inverted, N-term could be
ionized, but it doesn’t have to be.
NH3+-Q-F-K-COONH3+-Gln-Phe-Lys-COO-
First R is wrong, Asp can be ionized
or not.
NH3+-(not an AA)-I-D-COONH3+-(not an AA)-Ile-Asp-COO-
Correct, shown in trans conformation
NH3+-I-P-R-COONH3+-Ile-Pro-His-COO-
If Ser is deprotonated, then Cys and Nt
should be deprotonated, or if Cys and
Nt are protonated, then Ser should be
protonated too.
NH3+-S-C-H-COONH3+-Ser-Cys-His-COO-
Correct
NH3+-V-C-G-COO-/
NH3+-E-C-T-COONH3+-Val-Cys-Gly-COO-/
NH3+-Glu-Cys-Thr-COO6
I. Amino acid structures, drawn at pH 7:
II. List of amino acid side chain pKa’s:
Ionizable group
pKa
amino group (-NH3+)
9.8
aspartic acid side chain
4.0
arginine side chain
12.0
carboxylic acid group (-COOH) 2.3
cysteine side chain
9.0
glutamic acid side chain
4.0
histidine side chain
6.5
lysine side chain
11
serine side chain
13
tyrosine side chain
10
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