Amino Acids & Proteins
Shu-Ping Lin, Ph.D.
Instit te of Biomedical Engineering
Institute
Enginee ing
E-mail: splin@dragon.nchu.edu.tw
Website: http://web.nchu.edu.tw/pweb/users/splin/
http://web nchu edu tw/pweb/users/splin/
Date: 10.13.2010
Amino Acids
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Proteins are the basis for the major structural components of animal
and human tissue Æ Linear chains of amino acids residues
Amino Acids (AA): 1 central carbon atom + 4 subgroups {amino
group (—NH2), carboxyl group (—COOH), hydrogen atom, and
a distinctive side chain (R)}
Organic molecules serve as chemical messengers between cells or function
as important intermediates in metabolic processes.
„ Different R groups Æ Different properties and AA
„ Mirror-image forms (stereoisomers)
Æ L and D-isomers
„ Only L-amino acids are in proteins, D-amino
acids are widely in bacterial cell walls.
„ 300 AA in nature,
nature but only 20 of these in proteins
„ Not every protein contains all of the 20 AA types.
„ All proteins have an AA containing sulfur
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Make peptides and Proteins
Synthesis of Polypeptides & Proteins
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Amino group join to carboxyl group and lose one water molecule Æ
Condensation reaction (amide synthesis reaction) Æ Covalent bond
between 2 amino acid residues is called a peptide bond or amide bond Æ
Form backbone of the polypeptides and expose side chains “R”
R Æ Result
in proteins with intricate 3D structures and a remarkable range of functions
Polypeptides: linear polymers, a head-to-tail fashion, a sense of direction
“grow from amino group toward carboxyl group” (Amine end (N terminal) is
always on the left, while the acid end (C terminal) is on the right.
First/Start amino acids in most polypeptides is the sulfur
sulfur-containing
containing amino
acid, methionine (M, genetic code: AUG)
Primary sequence of amino acids in polypeptide affects shape and function
off proteins.
t i
Æ Many
M
proteins
t i are single
i l polypeptides.
l
tid
Other
Oth proteins
t i are
multiple polypeptides (form a complex), and multiple genes may be involved
Special Properties of Amino Acids
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Physical properties: a "salt-like"
salt like behavior,
behavior a variety of structural parts which
result in different polarities and solubilities
Crystalline solids with relatively high melting points, and most are quite
soluble
l bl in
i water and
d insoluble
i
l bl in
i non-polar
l solvents.
l
In solution, the amino acid molecule appears to have a charge which
changes
g with pH.
p
Intramolecular neutralization reaction leads to a salt-like ion called a
zwitterion.
A i acid
Amino
id has
h both
b th an amine
i and
d acid
id group neutralized
t li d in
i the
th zwitterion
itt i
Æ Neutral (unless there is an extra acid or base on the side chain)
The amino acids in the zwitterion form:
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Carboxyl group can lose a hydrogen ion to become negatively charged.
Amine group can accept a hydrogen ion to become positively charged.
Amino Acids with Hydrocarbon Chains
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Glycine
y
(gly,
(g y, G):
) simplest
p
AA with a hydrogen
y g atom as its side chain,, fits
into tight corners in the interior of a protein molecule
Alanine (Ala, A): with a methyl group (CH3) as its side chain
3 4 carbons
3~4
b
long:
l
V li
Valine
(Val,
(V l V),
V) Leucine
L
i
(Leu,
(L
L)
L), and
d Isoleucine
I l
i
(Ile, I), hydrocarbon side chains pack AA together to form compact
structures with few holes exposed to water and often interact with lipidcontaining membranes
Proline (Pro, P): the bends of folded protein chains, 3-carbon-atom
hydrocarbon side chain bound to both central carbon and nitrogen atom,
atom
very rigid, its presence creates a kink in a polypeptide chain
Aromatic Amino Acids
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Phenylalanine (Phe, F), Tryptophan (Trp, W) and
Tyrosine (Tyr, Y): side chains of aromatic rings.
Tryptophan (Trp, W) also contains a nitrogen atom in
its side chain.
Phenylalanine (Phe, F) and Tryptophan (Trp, W) are
strongly hydrophobic.
Tyrosine (Tyr, Y): less hydrophobic due to a hydroxyl
group
g
p (a
( potential
p
site of addition of a phosphate
p
p
group)
g p)
Amino Acids Containing Sulfur
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Cysteine
C
t i
(Cys,
(C
C) and
d Methionine
M thi i
(Met,
(M t M):
M) a sulfur
lf atom
t
in the side chains, hydrophobic
Side chain of Cysteine is highly reactive Æ Form a disulfide
links play a special role in shaping some proteins
Cysteine residues create folds and domains in the geometry
of proteins.
Methionine is the “START”
START codon in protein
protein-coding
coding genes.
Water-Loving (Hydrophilic) Amino Acids
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Serine (Ser,
(Ser S) and Threonine (Thr
(Thr, T): hydroxylated version of
Alanine and Valine; hydroxyl groups are more reactive, hydrophilic, and
potential sites of phosphate addition
Lysine (Lys, K), Arginine (Arg, R), and Histidine (His, H): polar
side chains containing nitrogen, highly hydrophilic
Side chains of Lysine and Arginine are the longest of the 20 amino acids
and normally positively charged.
Histidine can be uncharged or positively charged and found in active
sites of enzymes, where it can readily switch between these states to
catalyze the making and breaking bonds
Hydrophilic Amino Acids
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Aspartate (Asp, D) and Glutamate (Glu, E): polar,
negatively charged acidic side chains, carboxyl groups, exist at
physiological pH
Asparagine (Asn, N) and Glutamine (Gln, Q) are
uncharged derivatives of Aspartate and Glutamate: amine
group in place of carboxylate, polar molecules
Amine group of Asn is a potential site of addition of sugar
residues
20 Amino Acids
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20 amino acids vary
in size, charge,
capacity to form
hydrogen bonds with
other molecules. Æ
Important
determinant of the
diversity of proteins
Side chains which
have pure
hydrocarbon alkyl
groups (alkane
branches) or
aromatic (benzene
rings)
gs) are
a e nono
polar Æ
Hydrophobic,
p
include
examples
valine, alanine,
leucine, isoleucine,
phenylalanine.
Synthesis of 20 Amino Acids
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Bacteria: using carbon source and ammonium ions in water to
synthesize 20 amino acids
Plants: using nitrogen compounds and carbohydrates to make
amino acids
Animals:
l using sugars and
d ammonia to make
k amino acids
d
Essential amino acids: amino acids that humans cannot
synthesize,
nthe i e 8 amino
mino acids,
id 6 of them are
e hydrophobic
h d ophobi (large
(l ge
hydrocarbon side chains – valine, leucine, and isoleucine;
aromatic side chains – phenylalanine and tryptophan; sulfur
sulfurcontaining – methionine), 2 of them are hydrophilic (threonine
and lysine)
Essential amino acids can be obtained from diet, such as meat,
fish, milk, and eggs. (Plant sources only contain a partial set of
essential amino acids, such as beans (isoleucine and lysine).)
The Genetic Code
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mRNA consists of a linear sequence of such 3-letter
3 letter words called codons Æ
43=64 distinct codons
Protein-coding genes all begin with a START codon and terminate with a
STOP codon.
d
Æ START codon
d is
i methionine
thi i (M)
Arginine (R), leucine (L), and serine (S) are represented by 6 codons. Æ
Synonymous
y
y
„
M thi i (M) and
Methionine
d
tryptophan (W) are
represented by signal
codons each.
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First 2 letters in a codon are
primary determinants of AA
identity Æ GU- (valine), GG(glycine)
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U or C as 2nd nucleotide Æ
Hydrophobic Æ GU and GC
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3rd nucleotide is U or C Æ
Same amino acid Æ CAU
and CAC (Histidine)
Protein-Coding Gene
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DNA sequence representing the beginning segment of a
protein-coding
t i
di gene:
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Th complement
The
l
t mRNA
RNA sequence:
„
mRNA codons: AUG, AAC, GUU, and UAC Æ MNVY
Sickle-Cell Mutation in
Hemoglobin Sequence
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Hemoglobin molecules exist as single, isolated units in RBC,
whether oxygen bound or not
not, RBCs maintain basic disc shape,
shape
whether transporting oxygen or not
Oxy-hemoglobin
Oxy
hemoglobin is isolated, but de
de-oxyhemoglobin
oxyhemoglobin sticks
together in polymers, distorting RBC Æ Some cells take on
“sickle” shape
Protein Function
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Proteins are key players in our living systems.
systems
Not every protein contains all of the 20 AA types.
All p
proteins have an AA containing
g sulfur
Each protein folds into a unique three-dimensional structure defined by its
amino acid sequence.
P t i structure
Protein
t t
h
has a hierarchical
hi
hi l nature.
t
Protein structure is closely related to its function.
Protein structure prediction is a grand challenge of computational biology.
Manipulation of protein sequence through changes in amino-acid sequence
is a tool in modern drug design.
Protein structure usually described in terms of an organizational hierarchy:
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Primary structure: amino-acid sequence
Secondary structure: spatial arrangement of amino acids that are near one
another in the linear sequence
Tertiary structure: spatial arrangement of amino acids, dividing line between
secondary and tertiary structure is not precise
Quaternary structure: more than one polypeptide chain exhibit an additional
structure
Protein Structure
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Proteins are natural
polymer
l
molecules
l
l
consisting of amino
acid units
Primary structure (Amino acid sequence)
↓
Secondary structure （α-helix, β-sheet）
↓
Tertiary structure （Three-dimensional
structure formed
f
db
by assembly
bl off
secondary structures）
↓
Quaternary structure （Structure formed
by more than one polypeptide chains）
Basic Structural Units of Proteins:
Secondary
Seco
da y S
Structure
uc u e
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The chemical nature of the carboxyl and
amino groups of all amino acids permit
hydrogen bond formation (stability) and
hence defines secondary structures within the
protein.
The R group has an impact on the likelihood
of secondary structure formation (Proline is
an extreme case)
Helices and sheets: regular secondary
structures, but irregular secondary structures
exist and can be critical for biological function
α-helix turn right or left from N to C terminal:
only right-handed are observed in nature, can
be stretched for breaking and rearranging Hbond Æ Elastic
β-plated sheet: hydrogen bonding between
elements and peptide linkages when the
protein chains extend and lie next to another,
another
forming flat sheets
Secondary structures, α-helix
and β-sheet, have regular
hydrogen bonding patterns
hydrogen-bonding
patterns.
α-helix
β-sheet
Three-Dimensional Structure of Proteins
Tertiary structure:
„While backbone interactions define most of the secondary structure
interactions, it is the side chains that define the tertiary interactions
„Disulphide
p
linkages
g between cysteines
y
form the strongest
g
covalent bond in
tertiary linkages
„Quaternary structure:
„More than one polypeptide chain
„Noncovalent forces hold multiple polypeptide chains together to form
protein complex Æ Ionic bonds (i.e. Van der Waals forces: transient, weak
electrical attraction of one atom for another)
another), hydrophobic interactions
(clustering of nonpolar groups), hydrogen bonds
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Quaternary structure
Tertiary structure
3D Molecular Graphics of
Scallop Myosin I
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α-helix:
α
helix: corkscrew-like
corkscrew like rightright
handed, side chains (circular
cylinder)
y
) extending
g outward
from the peptide backbone
of the helix
β plated sheet: a flat arrow
β-plated
pointing toward the carboxyl
end of the peptide
p p
C
N
Gene
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A human cell contains about 100 million proteins of about
10,000 types Æ These cells all possess the same protein-coding
genes (~30,000),
( 30 000) b
butt diff
differentt cellll types
t
express different
diff
t
proteins of these genes Æ Complexity of the organism
Gene in vertebrate: Short sequences (exons) + long noncoding
sequences (introns)
Various spatial combinations of these exons correspond to
different proteins.
A gene can code for multiple proteins in higher forms of life
life.
Complicating proteins: proteins with carbohydrate, lipid,
phosphate,
p
p
, and other types
yp of attachments