Lecture 3

Question 1

At what rate do enzymes typically accelerate rxns?

Answer 1

10^6 - 10^12

Question 2

What do enzymes lower?

Answer 2

Activation energy, not overall energy of reaction

Question 3

How does hydrogen bonding in active site of enzyme interact with substrates?

Answer 3

1) orients substrates
2) source of protons
3) stabilize structure
4) modulate pKa of side chains

Question 4

How does electrostatic interactions (ion-ion and ion-dipole) in active site of enzyme interact with substrates?

Answer 4

1) orients substrates
2) modulate pKa of side chains
3) Stabilize charge build up

Question 5

How does hydrophobic interactions in active site of enzyme interact with substrates?

Answer 5

1) orients substrates
2) modulate pKa of side chains
3) Remove H2O from active site, which may interfere with reaction or create unwanted products by hydrolyzing substrate or product

Question 6

Arrhenius Eqn

Answer 6

K = Ae^(-Activ.Ener./RT)

Question 7

What is the Pauling Principle

Answer 7

Enzymes bind reaction transition state structures even more strongly than they bind the initial substrates

Question 8

Enzyme specificity

Answer 8

Between different compounds, enzyme active sites evolve to bind specific substrates (example: chymotrypsin that binds several different AA side chains that are similar)

Question 9

Enzyme selectivity

Answer 9

Within a compound, enzyme active sites orient substrates and control sites of reactivity allowing for extremely selective reactions (i.e. if there were two OH groups on a molecule, enzyme selectivity means that the enzyme has a means of orienting the substrate so that it only reacts with the OH group its supposed to and not any other similar groups within the compound)

Question 10

What are the roles of proteases (4)?

Answer 10

1) Digest proteins to yield peptides and/or amino acid monomers
2) Control cell growth
3) Programmed cell death
4) Maturation of proteins and / or signal transduction

Question 11

How do aspartyl proteases enhance the reactivity of water?

Answer 11

Hydrophobic pocket in enzyme active site raises pKa of aspartyl groups allowing them to function as acid/base catalysts. Makes water into better nucleophile through acid/base interactions between Asp groups, H2O and peptide.

Question 12

How does zinc protease enhance reactivity of water?

Answer 12

Zn2+ acts as lewis acid (accepts electrons) and draws e- away from H2O making the protons on H2O more acidic. Thus, Zn2+ lower the pKa of water to about 7 from 16.

Question 13

How do serine/cysteine proteases function as catalytic enzymes?

Answer 13

They use an initial nucleophile to make a more reactive electrophile intermediate.

Question 14

What is the function of the Asp - His interaction in Ser/Cys proteases?

Answer 14

Asp Ion-dipole interaction between O- on Asp and NH on His stabilizes the conjugate acid of His, thus enhancing His’s ability to act as base

Question 15

What is the purpose of the oxyanion hole in Ser/Cys protease?

Answer 15

Pocket in active site where backbone amides position the substrate and stabilize transition state/tetrahedtral intermediate

Question 16

Why is the acyl enzyme intermediate of Ser/Cys protease more reactive than amide?

Answer 16

In acyl intermediate, there is an ester instead of amide. O in ester is more e- withdrawing than N in amide, thus the carbonyl of acyl intermediate is more e- deficient and thus more electrophilic and more open to attack from water which is a poor nucleophile to complete hydrolysis.