Key Concepts
Most cell functions depend on proteins.
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
The Structure of Amino Acids
All proteins are made from just 20 amino acid building blocks.
• All amino acids have a central carbon atom that bonds to NH2, COOH, H, and a variable side chain (“R-group”).
The Nature of Side Chains
Functional Groups Affect Reactivity
• R-groups differ in their size, shape, reactivity, and interactions with water.
1. Nonpolar R-groups: hydrophobic; do not form hydrogen bonds; coalesce in water
2. Polar R-groups: hydrophilic; form hydrogen bonds; readily dissolve in water
• Amino acids with hydroxyl, amino, carboxyl, or sulfhydryl
Monomers and Polymers
• Many mid-size molecules, such as amino acids and nucleotides, are individual units called monomers. They link together
(polymerize) to form polymers, such as proteins and nucleic acids.
• Macromolecules are very large polymers made up of many monomers linked together.
Assembling and Breaking Apart Polymers
• Polymerization requires energy and is nonspontaneous.
• Monomers polymerize through condensation (dehydration) reactions, which release a water molecule.
• Hydrolysis is the reverse reaction, which breaks polymers apart by adding a water molecule.
• In the prebiotic soup, hydrolysis is energetically favorable and thus
would predominate over condensation. However, polymers
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 chain of amino acids linked by peptide bonds is called a
polypeptide.
– Polypeptides containing fewer than 50 amino acids are called oligopeptides (peptides).
Polypeptide Characteristics
• Within the polypeptide, the peptide bonds form a “backbone” with three key characteristics:
1. R-group orientation
– Side chains can interact with each other or water. 2. Directionality
– Free amino group, on the left, is called the N-terminus. – Free carboxyl group, on the right, is called the
C-terminus. 3. Flexibility
What Do Proteins Do?
Proteins are crucial to most tasks required for cells to exist:
– Catalysis – enzymes speed up chemical reactions.
– Defense – antibodies and complement proteins attack pathogens.
– Movement – motor and contractile proteins move the cell or molecules within the cell.
– Signaling – proteins convey signals between cells.
– Structure – structural proteins define cell shape and comprise body structures.
What Do Proteins Look Like?
Proteins can serve diverse functions in cells because they are
diverse in size and shape as well as in the chemical properties of their amino acids.
Primary Structure
• A protein’s primary structure is its unique sequence of amino acids.
• Because the amino acid R-groups affect a polypeptide’s properties
Secondary Structure
• Hydrogen bonds between the carbonyl group of one amino acid and the amino group of another form a protein’s secondary
structure.
– A polypeptide must bend to allow this hydrogen bonding, forming:
– -helices
– -pleated sheets
• Secondary structure depends on the primary structure.
– Some amino acids are more likely to be involved in -helices; others, in -pleated sheets.
Tertiary Structure
• The tertiary structure of 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 distinctive three-dimensional shape of the polypeptide.
• R-group interactions include hydrogen bonds, hydrophobic
R-group Interactions That Form Tertiary Structures
• Hydrogen bonds form between hydrogen atoms and the carbonyl group in the peptide-bonded backbone, and between hydrogen and negatively charged atoms in side chains.
• Hydrophobic interactions within a protein increase stability of
surrounding water molecules by increasing hydrogen bonding.
• van der Waals interactions are weak electrical interactions
between hydrophobic side chains.
• Covalent disulfide bonds form between sulfur-containing R-groups.
Quaternary Structure
Summary of Protein Structure
• Note that protein structure is hierarchical.
– Quaternary structure is based on tertiary structure, which is based in part on secondary structure.
– All three of the higher-level structures are based on primary structure.
• The combined effects of primary, secondary, tertiary, and
Folding and Function
• Protein folding is often spontaneous, because the hydrogen bonds and van der Waals interactions make the folded molecule more energetically stable than the unfolded molecule.
• A denatured (unfolded) protein is unable to function normally.
Prions and Protein Folding
• Prions are improperly folded forms of normal proteins that are present in healthy individuals.
– Amino acid sequence does not differ from a normal protein, but shape is radically different.
• Prions can induce normal protein molecules to change their
An Introduction to Catalysis
• Catalysis may be the most fundamental of protein functions.
• Reactions take place when:
– Reactants collide in precise orientation
– Reactants have enough kinetic energy to overcome repulsion between the electrons that come in contact during bond
formation
• Enzymes perform two functions:
1. Bring substrates together in precise orientation so that the electrons involved in the reaction can interact
Activation Energy and Rates of Chemical Reactions
• The activation energy (Ea) of a reaction is the amount of free energy required to reach the intermediate condition, or transition state.
• Reactions occur when reactants have enough kinetic energy to
reach the transition state.
– The kinetic energy of molecules is a function of their temperature.
• Thus, reaction rates depend on:
– The kinetic energy of the reactants
Catalysts and Free Energy
• A catalyst is a substance that lowers the activation energy of a reaction and increases the rate of the reaction.
• Catalysts lower the activation energy of a reaction by lowering the
free energy of the transition state.
Enzymes
• 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.
Enzymes:
1. Bring reactants together in precise orientations 2. Stabilize transition states
• Protein catalysts are important because they speed up the chemical
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 active site.
• Many enzymes undergo a conformational change when the substrates are bound to the active site; this change is called an induced fit.
The Steps of Enzyme Catalysis
• Enzyme catalysis has three steps: 1. Initiation
– Substrates 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
Do Enzymes Act Alone?
• Some enzymes require cofactors to function normally. These are either metal ions or small organic molecules called coenzymes.
Enzyme Regulation
• Competitive inhibition occurs when a molecule similar in size and shape to the substrate competes with the substrate for access to the active site.
• 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.
What Limits the Rate of Catalysis?
• Enzymes are saturable; in other words, the rate of a reaction is limited by the amounts of substrate present and available enzyme.
– The speed of an enzyme-catalyzed reaction increases linearly at low substrate concentrations.
– The increase slows as substrate concentration increases
– The reaction rate reaches maximum speed at high substrate
concentrations.
• All enzymes show this type of saturation kinetics.
Physical Conditions Affect Enzyme Function
• Enzymes function best at some particular temperature and pH. – Temperature affects the movement of the substrates and
enzyme.
Rate of Enzyme-Catalyzed Reactions
• To summarize, the rate of an enzyme-catalyzed reaction depends on:
1. Substrate concentration
2. The enzyme’s intrinsic affinity for the substrate 3. Temperature
