Professional Documents
Culture Documents
Subject: Biochemistry
Date: (Thursday) June19, 2014
Title: (1.1) Amino Acid & Protein Organization
Lecturer: Dr. Catherine C. Donato
Batch/section: 2018A
Sem/ A.Y.: 1st/A.Y. 2014-2015
Transcribers: Ang, Angeles, Aover, A. Aquino, and R.Aquino
Trans Subject head: Barona, F. (09164082972/fonsecabarona@gmail.com)
Evangelista, A. (09369390879 / AlanAEvangelista@gmail.com)
o
I.
Outline
A. Introduction to Proteins and Amino acids
B. Amino Acids
1. Structure
2. Functional Groups
3. Properties
C. Proteins
1. Structural Organization
2. Disease applications
D. Modifications
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II.
Objectives
At the end of the lecture, the student should be able to
know the...
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B. AMINO ACIDS
1. Structure
Lecture
Page 1 of 10
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Hydrogen atom
The fourth valency is linked to a specific
chemical group (Functional group)
A. Alkyl Group
H
O
H
+
NH3
H
Alanine (Ala, A)
Methyl group
Non-polar
Aliphatic
H3C
+
NH3
H3C
H3C
NH3
O
CH3
H
O
H3C
CH3
H
NH3
H3C
HO
NH3
H3C
2. Functional Groups
Constitute the R-side chain in the basic
amino acid structure
Determines the properties of the amino acid
NH3
Threonine (Thr, T)
Hydroxyl containing side
chain
Polar uncharged
C. Sulfur Group
O
H
O
HS
A.Y. 2014-2015
Leucine (Leu, L)
Isobutyl (-carbon)
Non-polar
Aliphatic
B. Hydroxyl Group
H
Serine (Ser, S)
O
hydroxymethyl
Polar uncharged
HO
Valine (Val, V)
Isopropyl group
Non-polar
Aliphatic
Isoleucine (Ile, I)
Isobutyl (-carbon)
Non-polar
Aliphatic
NH3
Glycine (Gly, G)
No side chain
Non-chiral
Non-polar
Aliphatic
Cysteine (Cys, C)
thiolmethyl
Polar uncharged
NH3
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Biochemistry | Amino Acids and Protein Organization
O
H
H3C
O
S
NH3
Methionine (Met, M)
Methyl ethyl thiol ether
Non-polar
Aliphatic
G. Aromatic Group
O
O
Phenylalanine (Phe, F)
Benzene ring
Non-polar
Aliphatic
NH3
H
O
HO
Tyrosine (Tyr, Y)
Phenol group
Polar uncharged
H
O
NH3
NH3
O
O
H
O
H
N
H
O
-
+
NH3
Tryptophan (Trp, W)
indole
Non-polar
Aliphatic
NH3
E. Amide Group
O
H
O
+
NH3
Glutamine (Gln, Q)
Amide containing side
chain
Polar uncharged
H. Looped/Cyclic Group
Proline (Pro, P)
O
H2+
Imino acid side chain
N
Non-polar
Aliphatic
O
NH2
O
O
H
O
H2N
+
NH3
Asparagine (Asn, N)
Amide containing side
chain
Polar uncharged
F. Amino Group
+
Lysine (Lys, K)
H3N
NH3
O
H
H2N
NH
Guanidino group
Positively charged
NH3
+
NH2
3. Properties
Group
Negatively
charged
(acidic)
Positively
charged
(basic)
Polar
uncharged
(hydrophilic;
easily
excitable)
Nonpolar
aliphatic
(hydrophobic;
linear)
Histidine (His, H)
H
N
O
+
N
H
H3N
Imidazole group
Positively charged
Aromatic
Characteristic
Additional carboxyl
group
Amino Acids
Glutamic acid,
Aspartic acid
Guanidino group
Imidazole
e amino grp
OH containing
Arginine
Histidine
Lysine
Serine,
threonine
Asparagine,
glutamine
Cysteine
Glycine
Proline
Alanine, valine,
leucine,
isoleucine
Methionine
Amide group
Thiol group
No side chain
Imino group
Hydrophobic alkyl
group
Thioether sulfur
atom
Bulky aromatic side
chains
Phenylalanine,
tyrosine,
tryptophan
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Biochemistry | Amino Acids and Protein Organization
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*Note:
Histidine contains a side chain that has a
five-member heterocyclic structure called the
imidazole group (pKa = 6.0 in solution)
at physiologic pH, the side chains of lysine
and arginine are fully ionized and positively
charged while histidine is weakly basic and
the free amino acid is largely uncharged
when histidine is incorporated into a protein,
the imidazole side chain can either be
positively charged or neutral depending on
the ionic environment provided (this is an
important property of histidine that contributes
to the role it plays in the functioning of
proteins such as myoglobin)
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d. Hydrophobic / Nonpolar
e. Aromatic Group
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Biochemistry | Amino Acids and Protein Organization
Ionic State
o All amino acids are at least dibasic acids
(presence of -amino acid and -carboxyl
groups), the ioncionic state being a function of
pH
o Net charge of the amino acid depends on the
environment pH
Zwitterions
o Amino acids are dipolar at neutral pH with a
net charge of 0
Acid-Base Properties
o Titration
Quantitative method of knowing the
concentration of a chemical solution
(analyte)
Via a reagent of known concentration
(strong alkali solutions ie. NaOH)known
as the titrant
to obtain titrable properties and to
separate amino acid
pK values
o Each amino acid has its own unique pK values
due to the R side chains
o Can be used to identify amino acids and how
they dissociate
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Biochemistry | Amino Acids and Protein Organization
Buffering capacity
o Buffers ability to resist change in pH when
C. PROTEINS
1. Structural Organization
The four levels of protein structure are
distinguished from one another by the degree of
complexity in the polypeptide chain
a) Primary
DNA-dependent: sequence of amino acids
determined by genes
o sequence determines protein folding,
folding determines protein function
involves release of water (dehydration
reaction)
limits rotation against each other because
they are coplanar
semi-rigid character is very important in the
higher order of protein structure
less steric hindrance if the trans form is
favored
pKa range
3.5 43.5 - 43.5 -4
Non -carboxyl
4 4.8
Imidazole
6.5 7.4
SH
8.5 - 9
OH
9.5 10.5
-amino
8-9
-amino
9.8 10.4
guanidinium
12
Table 4: pKa range of dissociating groups
Bond(s):
o Peptide chain
Linkage of amino acids by covalent bonds
-carboxyl group bonds with -amino
group of another amino acid via
dehydration process
These peptide bonds have a partial
double-bond character
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Biochemistry | Amino Acids and Protein Organization
Bond(s):
o Hydrogen bonds
Maintains structural integrity
Forms between 2 non-adjacent AAs
During coiling, they are at close proximity
Structure(s):
o -helix
most common type of secondary structure
right-handed
o -pleats
anti-parallel orientation
Figure 8: Peptide bond formation
Disulfide bonds
formed between the thiol (SH) groups of
two cysteines (oxidation reaction)
Structure(s):
o Linear
NH3+ to COO- (left to right)
Partial double bond
Coplanar, limits rotation
Cis/Trans configuration
Cis: R chains from 2 aa on the same
plane; less stable due to steric
hindrance
Trans: R chains from 2 AAs on
opposite planes; more stable, hence
more favored
b) Secondary
Spatial arrangement of polypeptide chain
(regular, repeating structural elements) that
functions to stabilize the protein
Van der Waals forces is seen in the
secondary structure; hydrogen bonds
maintain structural integrity of the proteins
together with the Van der Waals forces
c) Tertiary
Highest order for a monomeric protein and
biologically active
Bond(s):
o Between distant or non-adjacent amino acids
o Salt Bridges
Also known as ionic bridges
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Biochemistry | Amino Acids and Protein Organization
Intra-disulfide bonds
Formed between 2 cysteine residues
Hydrogen bonds
Formed between polar (hydrophilic)
residue chains
Hydrophobic interactions
Formed when 2 nonpolar groups are
attracted by a mutual repulsion of water
Includes van der Waals interaction
between 2 nonpolar aas
Structure(s):
o 3D arrangement of a single polypeptide chain
Interactions between R side chains are
important in tertiary folding of proteins
d) Quaternary
Interactions between 2 or more subunits
(tertiary structures) of multimeric proteins
Bond(s):
o Non-covalent bonds
Maintained by the same forces active in
tertiary structures; hydrophobic interaction
is the main stabilizing force
Structure(s):
o Homomeric
subunits are the same; multiple copies of
the same protein
o Heteromeric
made up of different subunits
Unstructured Proteins
o Proteins that do not follow the classical
structure; lack a stable folded structure
Chemical structure can be recognized
from the amino acid sequences of their
polypeptide
Biologic relevance the binding strength
of unstructured proteins to their binding
partners is generally weaker than for a
binding of a molecule to a preformed state
This property is often advantageous
as weak and transient interactions are
required for many biological
processes
2. Disease Applications (abnormalities in protein
structure)
Sickle Cell Anemia
o Caused by a single amino acid substitution
The underlying problem in sickle cell
anemia is that the valine for glutamic acid
substitution results in hemoglobin
tetramers that aggregate into arrays upon
deoxygenation in the tissues
This aggregation leads to deformation of
the red blood cell into a sickle-like shape
making it relatively inflexible and unable
to traverse the capillary beds
Alzheimers Disease
o Caused by protein misfolding
Due to the accumulation of abnormally
folded amyloid beta protein in the brain
*Proteins usually fold and unfold many
times as they carry out their tasks, and
each cycle is an opportunity for it to
misfold. When that happens, the body
generally destroys and discards the
useless protein. But when that process
fails, misfolded proteins can form the
gummy amyloid plaques
Creutzfeldt-Jakob disease
o Caused by abnormal protein
foldingsynthesis of prions death of brain
cells release of more prions to infect other
brain cells
o Prions can survive in nerve tissue, such as
the brain or spinal cord, for a very long time,
even after death
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Biochemistry | Amino Acids and Protein Organization
Phenylketonuria (PKU)
o An autosomal recessive disorder that results
from an accumulation of phenylalanine
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D. MODIFICATIONS
Protein synthesis occurs by a process known as
translation. After translation, proteins are further
modified, a process called posttranslational
modification.
These modifications change the structure of
amino acids in a way that may serve a regulatory
function, target or anchor the protein in
membranes, enhance a proteins association with
other proteins, or target it for degradation.
1. Hydroxylation/Oxidation
o Addition of a hydroxyl group to the protein
o Often facilitated by enzymes called
hydroxylases
o Principal residue to be hydroxylated is proline
o Important in making collagen flexible and rigid
(addition of OH to Proline)
2. Carboxylation
o Addition of a carboxyl group to the protein
o Important in blood clotting, bone growth, and
extraosseus calcification
o Mediated by calcium ions by binding to the two
negatively charged carboxyl groups of
gamma-glutamate and 2 additional negatively
charged groups provided by phospholipids in
the cell membrane
3. Denaturation
o Process of unfolding secondary, tertiary, and
quaternary protein structures (protein loses its
structure and function)
o Accomplished by change in environmental
conditions:
a change in pH
an increase in temperature
an increase in ionic strength from
concentrated inorganic salts
the addition of an organic solvent
4. Regulation
a) Phosphorylation
o is the addition of a phosphate (PO43)
group to a protein or other organic
molecule
o turns many protein enzymes on and off,
thereby altering their function and activity
(eg. Phosphorylation of an OH group on
serine, threonine, or tyrosine by a protein
kinase introduces a large, bulky,
negatively charged group that can alter
the activity of a protein
o Stimulates an enzyme
b) Acetylation
o the addition of an acetyl group, either at
the N-terminus of the protein or at lysine
residues
o Inhibits an enzyme
c) ADP-ribosylation
o is the transfer of an ADP-ribose from NAD
to an arginine, glutamine, or a cysteine
residue on a target protein in the
membrane (primarily in leukocytes,
skeletal muscles, brain, and testes). This
modification may regulate the activity of
these proteins
o These reactions are involved in cell
signaling and the control of many cell
processes, including DNA repair and
apoptosis
IV.
Guide questions
1. What are the polar amino acids? What are the nonpolar amino acids?
- Polar amino acids are: Cysteine, Serine,
Threonine, Tyrosine, Asparagine and Glutamine.
(Cysters Serine Threonine play TAG)
- *The non-polar amino acids are: Tryptophan,
Proline, Isoleucine, Glycine, Leucine,
Phenylalanine, Alanine, Valine, Methionine. (Three
pretty Indian girls like patient and valiant men.)
2. What are the types of interactions occur in tertiary
protein structures?
- Salt bridges, intra-disulfide bridges, hydrogen
bonding, hydrophobic interactions
3. What is a Zwitterion?
- The form of amino acids where the positive charge
on the amino group balances the negative charge
on the carboxyl group, which results in a net
charge of zero.
Page 9 of 10
Biochemistry | Amino Acids and Protein Organization
V.
Sources
Devlin, T. (2011). Textbook of Biochemistry with Clinical
Correlations, Wiley-Liss 7th Edition. New York: A
John Wiley & Sons, Inc., Publication.
Lehninger, A., et al. (2008). Principles of Biochemistry,
Worth Publishers 5th Edition. New York: W H.
Freeman and Company, Publication.
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Biochemistry | Amino Acids and Protein Organization