Proteins

What do they look like and what

do they do?
 First, what are proteins made of?
 Amino acids – 20 different ones

 All amino acids have a central carbon atom

that bonds to NH2, COOH, H, and a variable
side chain.

 In water (pH7), the amino and carboxyl groups

ionize to NH3+ and COO–, respectively—this
helps amino acids stay in solution and makes
them more reactive.
 The Nature of Side Chains
 The 20 amino acids differ only in the variable side chain or R-
group attached to the central carbon

 R-groups differ in their size, shape, reactivity, and interactions

with water.
(1) Nonpolar R-groups:

(2) Polar R-groups:

 Amino acids with hydroxyl, amino, carboxyl, or sulfhydryl

functional groups in their side chains are more chemically
reactive than those with side chains composed of only carbon
and hydrogen atoms.
20 Major
Amino
Acids
You are building a protein that you want to be
soluble in water. Based on the electronegativity of
the atoms, which of the functional groups would
you want in the amino acids of your protein?
You are building a protein that you want to be
soluble in water. Based on the electronegativity of
the atoms, which of the functional groups would
you want in the amino acids of your protein?

a) functional groups with C and H.

b) functional groups with H only.
c) functional groups with C, O and H.
d) Actually, no functional groups are polar.
 Condensation and Hydrolysis
Reactions
 Monomers polymerize through condensation reactions,
which release a water molecule.

 In the reverse reaction, hydrolysis, water reacts with a

polymer to release a monomer.

 Amino acids polymerize to form proteins.

 In the prebiotic soup, hydrolysis would predominate over

condensation because it is energetically favorable. However,
polymers on mineral particles such as clay or mud are
protected from hydrolysis.
 The Peptide Bond
 Condensation reactions bond the carboxyl group
of one amino acid to the amino group of another
to form a _________________________

 A _________ is flexible and has directionality

(the N-terminus has a free amino group and the
C-terminus has a free carboxyl group), and its
side chains extend out from the backbone.
 Peptide Bond Formation
Electrons shared between
carbonyl group and peptide
bond offer some characteristics
of double bonds

Peptide
Carboxyl Amino bond
group group
 What Do Proteins Do?
 The diverse functions of proteins include:
 What Do Proteins Look Like?
 Proteins are diverse in size and shape, as
well as in the chemical properties of their
amino acids.
 Proteins have four basic levels of structure:
 Primary Structure
 A protein’s primary structure is its
____________________________.

 Because the amino acid R-groups affect a

polypeptide’s properties and function, just
a single amino acid change can radically
alter protein function.
Polymer – molecule with
repeating subunits
 Secondary Structure
 Secondary structure results in part from hydrogen
bonding between the carboxyl oxygen of one amino acid
residue and the amino hydrogen of another. A
polypeptide must bend to allow this ____________
_____________________________________

 Secondary structure depends on the primary structure—

some amino acids are more likely to be involved in α-
helices; while others, in β-pleated sheets.

 Secondary Structure ________________by way of the

large number of hydrogen bonds.
Secondary Structures of
Proteins
Hydrogen bonds form between peptide chains.

Hydrogen bonds
Secondary structures of proteins result.

-helix -pleated
sheet
Ribbon diagrams of secondary structure.

Arrowheads
are at the
carboxyl end
of the arrows

-helix -pleated
sheet
 Tertiary Structure
 The tertiary structure of a polypeptide results from
interactions between R-groups or between R-groups and the
peptide backbone.

 R-group interactions include _____________, ___________

, covalent ______________, and_______________.

 Hydrogen bonds can form between hydrogen atoms and the

carboxyl group in the peptide-bonded backbone, and between
hydrogen atoms and atoms with partial negative charges in
side chains.
 Molecular Interactions
 _____________________ are electrical interactions
between hydrophobic side chains. Although these
interactions are weak, the large number of van der Waals
interactions in a polypeptide significantly increases
stability.

 ______________________ form between sulfur-

containing R-groups.

 __________ form between groups that have full and

opposing charges.
 Tertiary Structures of Proteins
Interactions that determine the tertiary structure of proteins

Hydrogen bond
between side chain
and carboxyl oxygen Ionic bond
Hydrophobic
interactions
(van der Waals
Hydrogen bond between interactions)
two side chains
Disulfide bond
 Tertiary Structures of Proteins
Tertiary structures are diverse.

A tertiary structure A tertiary structure composed A tertiary structure rich in

composed mostly of - mostly of -pleated sheets disulfide bonds
helices
 Quaternary Structure
 Some proteins contain several distinct
polypeptide subunits that interact to form a
single structure; .

 The combined effects of primary, secondary,

tertiary, and sometimes quaternary structure
allow for amazing diversity in protein form and
function.
 Quaternary Structures of
Proteins
Cro protein, a dimer Hemoglobin, a tetramer
You are asked to provide data that support the
hypothesis that protein structure and function are
correlated. The best set of data to support this
hypothesis is _____.
You are asked to provide data that support the
hypothesis that protein structure and function are
correlated. The best set of data to support this
hypothesis is _____.

a) unfolded proteins do not function normally

b) enzymes tend to be globular in shape
c) proteins function best at certain temperatures
d) proteins have four distinct levels of structure and many
functions
Changing primary sequence can alter
quaternary shape and hence function of
protein!
 Folding and Function
 Protein folding is often spontaneous, because the
hydrogen bonds and van der Waals interactions make
the folded molecule more stable energetically than the
unfolded molecule.

 A denatured (unfolded) protein is unable to function

normally.
 What Do Proteins Do?
 The diverse functions of proteins include:
 An Introduction to Catalysis
 Catalysis may be the most fundamental of protein
functions.

 Reactions take place when reactants collide in precise

orientation and have enough kinetic energy to overcome
repulsion between electrons that come in contact as a
bond forms.
 Reactions
 Reaction rates depend on the kinetic energy of the
reactants and the activation energy (Ea) required to
achieve the transition state.
 Reactions produce a ΔG – a difference in free energy
between reactants and products

 A catalyst ________the activation energy of a reaction by

lowering the free energy of the transition state. Catalysts __
______change ΔG and _______ consumed in the reaction.

 Enzymes are protein catalysts and typically catalyze only

one reaction. Most biological chemical reactions occur at
meaningful rates only in the presence of an enzyme.
How Do Enzymes Work?
Transition state

Activation energy

Reactants

Products
How Do Enzymes Work?
Transition state

Ea with
enzyme

Reactants

∆G does
not change Products
 How Do Enzymes Work?
 Enzymes bring substrates together in specific positions
that facilitate reactions, and are very specific in which
reactions they catalyze.

 Substrates bind to the enzyme’s ________, and

interactions between the enzyme and the substrate
stabilize the transition state and lower the activation
energy required for the reaction to proceed.
 Reactant Molecules Bind to
the Active Site

Substrate When the substrate

(glucose) binds to the enzyme’s
active site, the enzyme
changes shape slightly.
This “induced fit” results in
tighter binding of the
Enzyme substrate to the active site.
(hexokinase)
 Enzymes
Enzyme catalysis has three steps:
(1) Initiation: reactants are precisely oriented
as they bind to the active site.
(2) Transition state facilitation: interactions
between the substrate and active site R-groups
lower the activation energy.
(3) Termination: reaction products are
released from the enzyme.
Enzyme Action: A Three Step
Process
A MODEL OF ENZYME ACTION

Substrates

Enzyme

1. Initiation: Reactants bind to

the active site in a specific
orientation, forming an
enzyme-substrate complex.
Enzyme Action: A Three Step
Process
A MODEL OF ENZYME ACTION

Transition state

Shape changes

2. Transition state facilitation:

Interactions between enzyme
and substrate lower the
activation energy required.
Enzyme Action: A Three Step
Process
A MODEL OF ENZYME ACTION

Products

3. Termination: Products have

lower affinity for active site and
are released. Enzyme is
unchanged after the reaction.
R-groups Help Stabilize an
Enzyme’s Transition State
R-groups Help Stabilize an
Enzyme’s Transition State
 Do Enzymes Act Alone?
 Some enzymes require cofactors to function normally.
These are either metal ions or small organic molecules
called coenzymes.

 ______________ at a location other than the active site.

 How are Enyzmes Controlled?
(Regulated)
 Most enzymes are regulated by molecules that are not
part of the enzyme itself.

 Competitive inhibition occurs when

competes with the substrate for active site binding.

 Allosteric (non-competitive) regulation occurs

when
 Types of Enzyme Regulation
Competitive inhibition directly blocks the active site.

Competitive
inhibitor
When the
Substrate regulatory molecule
binds to the
enzyme’s active
site, the substrate
cannot bind
Enzyme
 Types of Enzyme Regulation
Allosteric regulation occurs when a regulatory molecule binds somewhere other than the active site.

Substrate
or
When the regulatory
molecule binds to a
Enzyme different site on the
enzyme, it induces a
shape change that
Regulatory
makes the active site
molecule
either available to the
substrate (left) or
Activating the enzyme Inactivating the enzyme unavailable (right)
Imagine an enzyme-catalyzed reaction proceeding
under typical conditions (for that enzyme). Which
of the following should you do to increase the rate
of the reaction?
 Imagine an enzyme-catalyzed reaction proceeding
under typical conditions (for that enzyme). Which
of the following should you do to increase the rate
of the reaction?

a) Add more substrate.

b) Add more product.
c) Increase the temperature by 20°C.
d) Lower the pH by 3.0.
 How Do Physical Conditions
Affect Enzyme Function?
 Enzymes function best at some particular
temperature and pH

(1) Temperature .

(2) pH affects the

There is an enzyme called pepsin that is released by
chief cells in the stomach and breaks down proteins
into amino acids in the stomach. You test the effect of
pH on the activity of this enzyme. You expect____.
There is an enzyme called pepsin that is released by
chief cells in the stomach and breaks down proteins
into amino acids in the stomach. You test the effect of
pH on the activity of this enzyme. You expect____.

a) no effect of pH on this enzyme, because pH typically

does not affect enzyme activity
b) maximum activity at pH 7, which is the typical pH of the
body
c) maximum activity at pH 2-3, which is the pH of the
stomach
d) maximum activity at pH 10
 Was the First Living Entity a
Protein?
 Several observations argue that the first self-replicating
molecule on Earth was a protein:

(1) Amino acids were abundant in the prebiotic soup.

(2) Proteins are the most efficient catalysts known.
(3) Self-replicating molecule had to act as a catalyst for
the assembly and polymerization of its copy.

 However, the first self-replicator probably needed to

have a mold or a template—something not found in
proteins.
 What you should have learned
in this chapter
 Proteins are made of amino acids. Amino acids vary in
structure and function.
 The structure of a protein can be analyzed at four levels:
(1) Amino acid sequence
(2) Substructures called -helices and -pleated sheets
(3) Interactions between amino acids that dictate a protein’s
overall shape
(4) Combinations of individual proteins that make up larger,
multiunit molecules
 In cells, most proteins are enzymes that function as
catalysts.