Download Life and Chemistry: Large molecules: Proteins

Biomolecules: Protein
structure and function
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Life and Chemistry: Large Molecules
Outline of today’s talk:
• Macromolecules: Giant Polymers
• Condensation and Hydrolysis Reactions
• Proteins: Polymers of Amino Acids
• Protein structure & function
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Macromolecules: Giant Polymers
• Macromolecules are giant polymers
(poly = “many”; mer= “unit”).
• Polymers are formed by covalent linkages of
smaller units called monomers.
• Molecules with molecular weights greater than
1,000 daltons (atomic mass units) are usually
classified as macromolecules.
Figure 3.3 Condensation and Hydrolysis of Polymers (Part 1)
• Macromolecules are made from smaller monomers by
means of a condensation or dehydration reaction in
which an OH from one monomer is linked to an H from
another monomer.
• Energy must be added to make a polymer.
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Condensation and Hydrolysis Reactions
The reverse reaction, in which polymers are broken back
into monomers, is a called a hydrolysis reaction.
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The Building Blocks of Organisms
26%
15%
7%
Water
70%
2%
2%
2%
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Macromolecules: Giant Polymers
• These macromolecules are made the same way
in all living things, and are present in all
organisms in roughly the same proportions.
• An advantage of this biochemical unity is that
organisms acquire needed biochemicals by eating
other organisms.
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Macromolecules: Giant Polymers
• The functions of macromolecules are related to their shape
and the chemical properties of their monomers.
• Some of the roles of macromolecules include:
 Energy storage
Carbohydrates
 Heredity
Nucleic Acids
Proteins:
 Structural support
 Transport
 Protection and defense
 Regulation of metabolic activities
 Means for movement, growth, development and more
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Amino acids
Amino acids have carboxyl and amino
groups—they function as both acid and
base.
a
Amine
Carboxyl
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Amino acids
Amino acids have carboxyl and amino
groups—they function as both acid and
base.
a
H3N+ H+ +
 -COO- + H+
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Amino Acids
Amino acids have carboxyl and amino
groups—they function as both acid and
base.
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Amino Acids
The side chains or R-groups also have
functional groups.
Amino acids can be grouped based on
side chains.
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Classes of Amino Acids
• Amino acids can be classified based on the characteristics
of their R groups.
 Five have charged hydrophilic side chains.
 Five have polar but uncharged side chains.
 Seven have hydrophobic side chains.
 Cysteine has a terminal disulfide (—S—S—).
 Glycine has a single hydrogen atom as the R group.
 Proline has a modified amino group that forms a
covalent bond with the R group, forming a ring.
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Charged Amino Acids
Hydrophilic “Water-loving”
These hydrophylic amino acids attract ions of opposite charges.
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Polar uncharged Amino Acids
Hydrophylic amino acids with polar but uncharged side chains
form hydrogen bonds
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Non polar Amino Acids
Hydrophobic amino acids
Hydrophobic = “Water-hating”
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Special Amino Acids
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Disulfide Bridges
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L- Amino Acids
The  carbon atom is asymmetrical.
Amino acids exist in two isomeric forms:
• D-amino
acids (dextro, “right”)
acids (levo, “left”)—this form is
found in organisms
• L-amino
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Optical isomers
Optical isomers result from asymmetrical carbons.
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Proteins are polymers of Amino Acids
• Proteins are synthesized by condensation
reactions between the amino group of one amino
acid and the carboxyl group of another. This forms
a peptide-linkage.
• Proteins are also called polypeptides. A
dipeptide is two amino acids long; a tripeptide,
three. A polypeptide is multiple amino acids long.
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Peptide bond
Amino acids bond together covalently by peptide bonds to
form the polypeptide chain.
Dehydration
reaction
Dipeptide
The peptide bond is inflexible—no rotation is possible.
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Peptide bond
• A proteins (polypeptides) has a backbone with
side chains extending from it
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Peptide bond
• Proteins (polypeptides) are chains with Amino (N)
terminus and Carboxyl (C) terminus
• A proteins amino-acid sequence is written from N to C.
Direction
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Proteins
• Proteios (Greek) first place
• Proteins are polymers of amino acids.
• The building blocks (amino acids) are common to all
organisms
• Proteins are molecules with diverse structures and
functions.
• Each different type of protein has a characteristic
amino acid composition and order.
Amino acids
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Proteins: Polymers of Amino Acids
• Proteins are polymers of amino acids. They are molecules with
diverse structures and functions.
• Each different type of protein has a characteristic amino acid
composition and order.
• Proteins are also called polypeptides. A dipeptide is two amino
acids long; a tripeptide, three. A polypeptide is multiple amino
acids long.
• <30aa = Peptide; >30aa = Protein
• Largest proteins - ~10,000aa
• Typical protein - 50-2000aa
Amino acids
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Proteins: Polymers of Amino Acids
• There are only 20 amino acids but the theoretical
number of different proteins is ENORMOUS:
20X20 = 400 distinct di-peptides
A protein comprised of 100 amino acid is a small
protein.
20100 Different small proteins (more than all the
electrons in the entire universe!).
Amino acids
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Proteome
• Proteome-the entire protein complement of the
organism
• Yeast = ~6000 different proteins
• Human=~30-40,000 different basic proteins with
many variations
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A protein’s specific shape determines its function
• A protein’s specific shape determines its function
• A protein consists of one or more polypeptide chain
Folded into a unique shape that determines the protein’s
function
Folding
Nitrogenase, catalyzes biological nitrogen fixation (N2 to NH3)
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Proteins have many possible structures
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Noncovalent Interactions within Proteins
Folding of proteins into
their final structure is
directed by non-covalent
interactions
More interactions = more stable conformation
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Molten globe
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Hydrogen bonds in proteins
04_06_Hydrogen bonds.jpg
Can form in any protein
Responsible for secondary structures
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Hydrogen bonds in proteins
Between side-chain and backbone
Between side-chains
Between atoms of backbone
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Protein secondary structures
• Hydrogen bonds Between atoms of backbone
help proteins fold into characteristic structures
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Beta sheet
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Protein secondary structures
• b pleated sheets are peptide regions that lie parallel to
each other.
• Sometimes the parallel regions are in the same peptide,
sometimes the parallel regions are from different peptide
strands.
• This sheet-like structure is stabilized by hydrogen bonds
between N-H groups on one chain with the C=O group on
the other.
• Spider silk is made of b pleated sheets from separate
peptides.
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Alpha Helix
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Alpha Helix
• The a helix is a right-handed coil.
• The peptide backbone takes on a helical shape due to
hydrogen bonds.
• The R groups point away from the peptide backbone.
• Fibrous structural proteins have a-helical secondary
structures, such as the keratins found in hair, feathers,
and hooves.
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Four levels of protein structure
• There are four levels of protein structure: primary,
secondary, tertiary, and quaternary.
• The precise sequence of amino acids is called its
primary structure.
• secondary structures consists of regular,
repeated patterns in different regions of the
polypeptide chain.
• A protein’s tertiary structure is the overall threedimensional shape (conformation) of a polypeptide
• When a polypeptide assembles into a complex with
additional proteins it acquires a Quaternary
Structure.
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Primary structure
A protein’s primary structure is the sequence of
amino acids forming its polypeptide chains
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Secondary structure
• secondary structures consists of regular, repeated
patterns in different regions of the polypeptide chain.
• This shape is influenced primarily by hydrogen bonds
arising between atoms within the polypeptide’s
repeating (N-C-C-N-C-C…) backbone
• Two common secondary structures are the a helix
and the b pleated sheet.
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Tertiary structure
• Tertiary structure is the overall three-dimensional shape
(conformation) of a polypeptide
• The primary determinants of the tertiary structure are the
interaction between R groups (side chains).
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Factors determining tertiary structure
Factors determining tertiary structure:
• The nature and location of secondary structures
• Hydrophobic side-chain aggregation and van der Waals
forces, which help stabilize them
• The ionic interactions between the positive and negative
charges deep in the protein, away from water
Ionic bonds between
charged R groups
Hydrophobic
interactions
Hydrogen
Interactions
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Coiled coil motif
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Disulfide bridges
Disulfide bridges, which form between cysteine residues
can also contribute to stabilization of tertiary structure.
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N.K.
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• Hair styling chemistry
Figure 3.6 The Four Levels of Protein Structure (Part 3)
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Quaternary Structure
• Quaternary structure results from the ways in
which multiple polypeptide subunits bind together
and interact.
• This level of structure adds to the threedimensional shape of the finished protein.
• Hemoglobin is an example of such a protein; it
has four subunits.
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Proteins: Polymers of Amino Acids
• It is now possible to determine the complete
description of a protein’s tertiary structure.
• The location of every atom in the molecule is
specified in three-dimensional space.
Figure 3.7 Three Representations of Lysozyme
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Proteins: Polymers of Amino Acids
• Shape is crucial to the functioning of some
proteins:
 Enzymes need certain surface shapes in order
to bind substrates correctly.
 Carrier proteins in the cell surface membrane
allow substances to enter the cell.
 Chemical signals such as hormones bind to
proteins on the cell surface membrane.
• The combination of attractions, repulsions, and
interactions determines the right fit.
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Hemoglobin can bind Oxygen
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Protein structure can change with function
Protein structure can change with function
• Hemoglobin first binds one O2
molecule
• Conformational changes, ionic
bonds are broken
• Exposure of buried side chains
• Enhanced binding of additional
O2
• The opposite happens when
hemoglobin releases its O2
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Sickle-cell Anemia
normal
disease
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Sickle cell anemia
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Proteins: Polymers of Amino Acids
• Changes in temperature, pH, salt concentrations,
and oxidation or reduction conditions can change
the shape of proteins.
• This loss of a protein’s normal three-dimensional
structure is called denaturation.
Structural information
is in the sequence
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Proteins: Polymers of Amino Acids
• Chaperonins are specialized proteins that help
keep other proteins from interacting
inappropriately with one another.
• When a protein fails to fold correctly, serious
complications can occur.
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Proteins: Polymers of Amino Acids
Some chaperonins help folding; some prevent
folding until the appropriate time.
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Aspirin, drug design
Hippocrates 5th Century B.C
Willow (bark)
Arthritis
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Aspirin, drug design
Salicin, Converted after digestion
into Slicylic acid (1700s)
Willow (bark)
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Aspirin, drug design
1897 Felix Hoffmann developed Aspirin
(Acetyl salicylic acid)
1971 Mechanism of action discovered by
the British pharmacologist, John Robert
Vane (awarded both a Nobel Prize in
1982).
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Aspirin, drug design
Felix Hoffmann
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Aspirin, drug design
Aspirin blocks Cyclooxygenase active site.
Cyclooxygenase (Cox) is required for prostaglandin production
and inflammation
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Aspirin, drug design
Cox 2 is responsible for prostaglandin production in
inflammation and pain
Aspirin Side effects in stomach are mediated by Cox1
Cox2
Cox1
Cox2 selective inhibitors
Celebrex
Vioxx
(Pfizer)
(Merck)
Table 3.1 The Building Blocks of Organisms
26%
15%
7%
Water
70%
2%
2%
2%