nucleic acid and the rna world

8/13/2019 Nucleic acid and the RNA world

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Chapter 3

Protein Structure and Function


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Early Origin-of-Life ExperimentsCould the first steps of chemical evolution have

occurred on ancient Earth?

To find out, Stanley Miller combined methane (CH4),

ammonia (NH3), and hydrogen (H2) in a closed system with

water, and applied heat and electricity as an energy

source.

The products included hydrogen cyanide (HCN) and

formaldehyde (H2CO), important precursors for more-

complex organic molecules and amino acids.

In more recent experiments, amino acids and other organic

molecules have been found to form easily under these

conditions. (prebiotic soup)


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Stanley Millers

experiment


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What Do Proteins Do?


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The Structure of Amino Acids

All proteins are made from just 21 amino acids.

All amino acidshave a central carbon atom (valance of4)that bonds to

-NH2 amino function group

-COOH carboxyl function group

-H hydrogen atom

- variable side chain (R group).

In water (pH7), the amino and carboxyl groups ionize toNH3+(base) and COO(acid), respectivelythis helpsamino acids stay in solution and makes them morereactive.


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The Nature of Side Chains The 21 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) Non polar R-groups: hydrophobic; Do not formhydrogen bonds; coalesce in water

(2) Polar R-groups: hydrophilic; Form hydrogen bonds;

readily dissolve in water

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.


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20 Major Amino Acids


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Condensation and Hydrolysis Reactions


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Condensation and Hydrolysis Reactions

Amino acids polymerizeto form proteins. Polymerizationreactions require energy and are not spontaneous.

Monomers polymerize through condensation reactions,

which release a water molecule. In the reverse reaction,hydrolysis, water reacts with a polymer to release amonomer.

In the prebiotic soup, hydrolysis would predominate overcondensation because it is energetically favorable.However, polymers on mineral particles such as clay ormud are protected from hydrolysis.


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The Peptide Bond

Condensation reactions bond the carboxyl group of one

amino acid to the amino group of another to form a

peptide bond.

A polypeptideis 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.


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Peptide Bond Formation

Carboxylgroup

Aminogroup Peptidebond

Electrons shared between

carbonyl group and peptide

bond offer some characteristics

of double bonds


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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,secondary, tertiary, and quaternary.


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Primary Structure

A proteins primary structure is its unique sequence of

amino acids.

Because the amino acid R-groups affect a polypeptidesproperties and function, just a single amino acid change

can radically alter protein function.


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Secondary Structure

Secondarystructureresults in part from hydrogen

bonding between the carboxyl oxygen of one amino acid

residue and the amino hydrogen of another. Apolypeptide must bend to allow this hydrogen bonding

thus, -helicesor -pleated sheets are formed.

Secondary structure depends on the primary structuresome amino acids are more likely to be involved in -

helices; while others, in -pleated sheets.

Secondary Structure increases stability by way of thelarge number of hydrogen bonds.


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Secondary Structures of ProteinsHydrogen bonds form between peptide chains.

Secondary structures of proteins result.

-helix -pleatedsheet

-helix -pleatedsheet

Ribbon diagrams of secondary structure.

Hydrogen bonds

Arrowheads

are at the

carboxyl end

of the arrows


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Tertiary Structure

The tertiarystructureof a polypeptide results from

interactions between R-groups or between R-groups and

the peptide backbone. These contacts cause the

backbone to bend and fold, and contribute to the 3D

shape of the polypeptide.

R-group interactions include hydrogen bonds, van der

Waals interactions, covalent disulfide bonds, and ionic

bonds.

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.


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Tertiary Structures of Proteins

Tertiary structures are diverse.

Interactions that determine the tertiary structure of proteins

A tertiary structure composed

mostly of -helicesA tertiary structure composed

mostly of -pleated sheetsA tertiary structure rich in

disulfide bonds

Ionic bond

Disulfide bond

Hydrophobic

interactions(van der Waals

interactions)Hydrogen bond betweentwo side chains

Hydrogen bond

between side chain

and carboxyl oxygen


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Van der Waals Interactions

van der Waals interactions are electrical interactions

between hydrophobic side chains. Although theseinteractions are weak, the large number of van der Waals

interactions in a polypeptide significantly increases

stability.

Covalent disulfide bonds form between sulfur-containing

R-groups.

Ionic bonds form between groups that have full andopposing charges.


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Quaternary Structure

Some proteins contain several distinct polypeptide

subunits that interact to form a single structure; the

bonding of two or more subunits produces quaternary

structure.

The combined effects of primary, secondary, tertiary, and

sometimes quaternary structure allow for amazing

diversity in protein form and function.


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Quaternary Structures of Proteins

Cro protein, a dimer Hemoglobin, a tetramer


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Folding and Function

Protein folding is often spontaneous, because the

hydrogen bonds and van der Waals interactions makethe folded molecule more stable energetically than the

unfolded molecule.

A denatured(unfolded) protein is unable to functionnormally.

Proteins called molecular chaperoneshelp proteins fold

correctly in cells.


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Activation Energy and Enzymes


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An Introduction to Catalysis

Catalysismay 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.

Enzymes bring substratestogether in precise orientation

so that the electrons involved in the reaction can interact.

Enzymes also affect the amount of kinetic energy

reactants must have for the reaction to proceed.

R ti R t


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Reaction Rates

Reaction rates depend on the kinetic energy of thereactants and the activation energy (Ea) required to

achieve the transition state).

Reaction rates depend on both the kinetic energy of thereactants and the activation energy of the reaction, or thefree energy of the transition state.

A catalyst lowers the activation energy of a reaction bylowering the free energy of the transition state. Catalystsdo not changeGand are not consumed in the reaction.

Enzymes are protein catalysts and typically catalyze onlyone reaction. Most biological chemical reactions occur atmeaningful rates only in the presence of an enzyme.


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How Do Enzymes Work?

Transition state

ReactantsProducts

Activation energy


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How Do Enzymes Work?

Enzymes bring substratestogether in specific positions

that facilitate reactions, and are very specific in which

reactions they catalyze.

Substrates bind to the enzymes activesite, and

interactions between the enzyme and the substrate

stabilize the transition state and lower the activation

energy required for the reaction to proceed.

En mes


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Enzymes

R-groups in the active site may form short-lived covalent

bonds that assist with the transfer of atoms or groups ofatoms from one reactant to another.

Enzymes induce the formation of the transition state toincrease reaction rates.

Enzyme catalysis has three steps:

(1) Initiation:reactants are precisely oriented as theybind to the active site.

(2) Transition state facilitation:interactions betweenthe substrate and active site R-groups lower theactivation energy.

(3) Termination:reaction products are released from the

enzyme.


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Enzyme Action: A Three Step Process

A MODEL OF ENZYME ACTION

Substrates

Enzyme

Transition state

Shape changes

Products

1.Initiation: Reactants bind tothe active site in a specific

orientation, forming an

enzyme-substrate complex.

2.Transition state facilitation:Interactions between enzyme

and substrate lower the

activation energy required.

3.Termination: Products havelower affinity for active site

and are released. Enzyme is

unchanged after the reaction.

D E A t Al ?


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Do Enzymes Act Alone?

Some enzymes require cofactorsto function normally.

These are either metal ions or small organic moleculescalled coenzymes.

Most enzymes are regulated by molecules that are not

part of the enzyme itself.

Competitive inhibitionoccurs when a molecule similar

in size and shape to the substrate competes with the

substrate for active site binding.

Allosteric regulation occurs when a molecule causes a

change in enzyme shape by binding to the enzyme at a

location other than the active site.


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Types of Enzyme RegulationCompetitive inhibition directly blocks the active site.

Competitive

inhibitorSubstrate

Enzyme

Allosteric regulation occurs when a regulatory molecule binds somewhere other than the active site.

Substrate

EnzymeRegulatorymolecule

Activating the enzyme Inactivating the enzyme

When the

regulatory molecule

binds to the

enzymes active

site, the substrate

cannot bind

When the regulatory

molecule binds to a

different site on the

enzyme, it induces a

shape change that

makes the active site

either available to the

substrate (left) or

unavailable (right)

or

Wh t Li it th R t f C t l i ?


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What Limits the Rate of Catalysis?

In enzymatic reactions, the rate of product formation

increases linearly for a given increase in substrateconcentration at low substrate concentrations, but levels

out at high substrate concentrations.

All enzymes show this type of saturation kinetics. High substrate affinity: achieves maximum reaction rate

rapidly as substrate concentration increases.

Low substrate affinity: achieves maximum rate only afterreaching high substrate concentrations.


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How Do Physical Conditions Affect Enzyme

Function?

Enzymes function best at some particular temperature

and pH

(1) Temperature affects the movement of substrates and

enzyme.

(2) pH affects the enzymes shape and reactivity.


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Key Concepts 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

proteins overall shape

(4) Combinations of individual proteins that make uplarger, multiunit molecules

In cells, most proteins are enzymes that function as

t l t

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