1.

2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Q: How many amino acids are there?

The twenty alpha-amino acids that are encoded by the

genetic code share the generic structure

Atom nomenclature within amino acids

(as used within the PDB)
O
N

CA
C
CB

CG2

OG1

Atom nomenclature within amino acids (as used within the PDB)

- The alpha carbon (CA) is immediately adjacent the most oxidized

carbon (which is the CO2- in amino acids)
- All the other heavy nuclei are named according to the Greek
alphabet.
-Put otherwise, LYS can be described by: CA, CB, CG, CD, CE, and NZ.

Lys
To Do: Learn how to name the atoms of all amino acids.
Hint: look at any generic PDB file to get a list of atom types.

Arg

Numbers are used to discriminate between similar positions

CB

CB

CB

CG

CG
CD1

CG2

CD2

OG1

OD1

ND2

Here are some harder examples

CB

CB
CD1

CG
CD2
NE2

ND1
CE1

CE2

CG

CZ

CB

CD2

CD2

CG

CE2

CD1

OH

NE1

CE2

CE3
CZ3
CH2
CZ2

Side-chain torsion angles

- With the exception of Ala and Gly, all sidechains
also have torsion angles.
- To Do on your own:
- Count the # of chis in each amino acid.
- Determine why Ala doesnt have a chi angle.

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Fischer
projection

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Terminologies

Hydrophobic: Amino acids are those with side chains that do not like
to reside in an aqueous environment. Hence, these amino acids buried
within the hydrophobic core of the protein.
Aliphatic: Hydrophobic group that contains only carbon or hydrogen atoms.
Aromatic: A side chain is considered aromatic when it contains an aromatic
ring system.

Polar: Polar amino acids are those with side-chains that prefer to
reside in an aqueous environment and hence can be generally found
exposed on the surface of a protein.

Twenty Amino acids

TYR: Amphipathic
GLY: Unclassifiable

Hydrophobic (non polar)

Aliphatic
(ALA, VAL, LEU, ILE,
MET, PRO)

Polar

Aromatic
(PHE, TRP)

Polar Neutral

Amide
(ASN, GLN)

-OH
(THR, SER)

-SH

Charged

Acidic

(CYS) (ASP, GLU)

Basic

(HIS,
LYS,ARG)

Its actually a bit more complicated

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Uncommon amino acids also have important functions

prothrombim,
a # of Ca+ binding proteins

plant cell wall,

collagen

elastin

collagen

Lysine
residues
myosin

Residues created by modification of common residues already incorporated into a polypeptide

rare, introduced during protein
synthesis rather than created
through a postsynthetic modification

~ 300 additional amino acids

have been found in cells

Reversibleaminoacidmodificationsinvolvedinregulationofproteinactivity
Phosphorylationisthemostcommontypeofregulatorymodification.

Not uncommon amino acids in biochemistry, but they are not encoded
within the genetic code (meaning not incorporated into proteins)

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Amino acids can act as acids and bases

Nonionic and zwitterionic forms
of amino acids

Titration of glycine

Titration curves predict the

electric charge of amino acids
Isoelectric point (or isoelectric pH)

amphoteric
(ampholytes - amphoteric electrolytes

pI = (pk1 + pk2) = (2.34 + 9.60) = 5.97

Amino acids differ in their acid-base properties

Amino acids with
R groups that do not ionize

pka of the COOH group: 1.8 2.4

pka of the NH3+ group: 8.8 11.0

Amino acids with ionizable R groups

e.g.

three stages (three ionization steps three pka values)

Effect of chemical environment on pKa

Peptides are chains of amino acids

Pentapeptide

hydrolysis

condensation

Two amino acid molecules can be

covalently joined through a substituted
amide linkage, termed a peptide bond,
to yield a dipeptide

Serylglyciltyrosylalanylleucine
or
Ser-Gly-Tyr-Ala-Leu
or
SGYAL

Peptides are named beginning with the amino-terminal

residue, which by convention is placed at the left.

just a few residues oligopeptide

many residues polypeptide

Biologically active peptides and polypeptides occur in a vast range of sizes

If at least two chains are identical the protein

bunit proteins: haveistwo
or to
more
said
be oligomeric, and the identical units
ptide chains associated
noncovalently
(consisting
of one or more chains) are referred to
as protomers.

The vast majority of naturally occurring proteins contain fewer than 2,000 amino acid residues.

BAHAN UTS SAMPAI SINI

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Primary structure = the complete set of covalent bonds within a protein

Polypeptides
Linear arrangement of n amino acid residues linked by peptide bonds.
Polymers composed of two, three, a few, and many amino acid residues are called
as dipeptides, tripeptides, oligopeptides and polypeptides.
Proteins are molecules that consist of one or more polypeptide chains.

Q: why is the pentapeptide SGYAL different than LAYGS?

Amino acid to Dipeptide

Amino Acid

Amino Acid

Note: this
chemistry will not
work as drawn!

Peptide bond
Peptide bond is the amide linkage that is formed between two amino
acids, which results in (net) release of a molecule of water (H 2O).
The four atoms in the yellow box form a rigid planar unit and, as we will
see next, there is no rotation around the C-N bond.

The peptide bond has a partial double

bond character, estimated at 40% under
typical conditions. It is this fact that
makes the peptide bond planar and rigid.

Aquickaside

..

+
+
Ahorribleleavinggroup

..

+
+
Aviableleavinggroup

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

1.
2.
3.
4.
5.
6.
7.
8.

Overall amino acid structure

Amino acid stereochemistry
Amino acid sidechain structure & classification
Non-standard amino acids
Amino acid ionization
Formation of the peptide bond
Disulfide bonds
Comparing protein sequences to describe evolutionary
processes.

Multiple sequence alignments

Given the sequences:

INDUSTRY
INTERESTING
IMPORTANT
One example of a MSA is:

IN-DUST--RY
INTERESTING
IMPOR--TANT

But is it better than:

INDU--ST-RY
INTERESTING
IMPOR-T-ANT

Multiple sequence alignments

I-N-DU-ST-RY
I-NTERESTING
IMPO-R--TANT

I--NDU-ST-RY
I--NTERESTING
I-MPO-R--TANT

IN-DUTS--RY
INTERESTING
IMPOR--TANT

INDU--ST-RY
INTERESTING
IMPOR-T-ANT

I-NDUS--T-RYINT-ERES-TING
IMPOR--TAN--T

I-N-D-U-S-T-RY
I-NTERE-S-TING
IMPO-RTA-NT---

Multiple sequence alignments

Possible MSA

Entire column can NOT have only gaps!

I-N-DU-ST-RY
I-NTERESTING
IMPO-R--TANT
Can NOT move residues around

I--NDU-ST-RY
I--NTERESTING
I-MPO-R--TANT
Possible

IN-DUTS--RY
INTERESTING
IMPOR--TANT

INDU--ST-RY
INTERESTING
IMPOR-T-ANT

Nothing matches!

Too many opening gaps!

I-NDUS--T-RYINT-ERES-TING
IMPOR--TAN--T

I-N-D-U-S-T-RY
I-NTERE-S-TING
IMPO-RTA-NT---

Which alignment pairs make the most sense?

More similar amino acids

AVGTLE
VLASID
VS.
AVGTLE
EKWVKV

A-VT-G-R-L-E
AA-TA-Q-V-IE
VS.

AVWF----VLIM
ALWFAMVFILIM
VS.

AVTG-RLE
AATAQ-IE

ESQG----KTD
DTQADGKCRTD

Fewer gaps

Gap location makes more sense

A multiple sequence alignment:

-CAPSRPLNENDDGR-QAFELIGTAVNM...
-CVPGRGEMEHDD-RDQVLELFGTVVNL...
-AVPKRAALQNDDGR-QGWELYGTVSAQ...
-AVPTKMNCFNDDGR-QSVNLIGTVSGN...
-ILPARTSMCNDDGR-QTIEMKGTPAGG...
--APGK--NGHKLV--Q-FELKGTYSRT...
AFAPRRIKMVNKLGR-QNFTLLGTFERT...
AYRPDRCNTCNKLGR-QDVELMGTDART...
-YRPEEWFGENKLGR-QSAELIGTDERS...
--APL-ETYWPKLGR-QTGALAGTNSAV...
--RPY-KAGWNKLGR-QSYELGGTNPYI...
---PARAKNMG---R-QSYHL--TMEWQ...

O
O
CH2OH
O
CH2-P

O
H
CHO

N
H

O
CH2 -P