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61 Cards in this Set

  • Front
  • Back

Describe a ping-pong double displacement reaction

One or more products are released before all substrates

1st substrate binding --> 1st release, 2nd substrate binding --> second released

Describe an ordered sequential reaction

All reactants bind in before the reaction occurs

What reaction type is defined by the existence of a substituted enzyme intermediate?

Ping-pong reaction

How does a complementarity pocket contribute to catalysis?

Complementarity pocket stabalizes the substrate

What are the 6 catalytic mechanisms of enzymes?

1) Proximity and orientation

2) preferential binding of the transition state complex

3) Catalysis by destabalization of substrate

4) Acid-base catalysis

5) Covalent catalysis (E+ and Nu: catalysis)

6) Metal Ion catalysis

What side chains are commonly used in acid-base catalysis?

AA's with pK's in the physiological range

Asp, Glu, His, Cys, Tyr, and Lys

What AA's are common nucleophiles?

Histidine's imidazole group

Unprotonated Lys

Thiol of Cys

Carboxyl group of Asp

Hydroxyl of Ser

What are common electrophiles from AA groups?


Protonated Imine C=NH+


What amino acids make up the catalytic triad?

Asp, His, and Ser

What is the role of the Asp in the catalytic triad?

Hydrogen bond donor to N-H of Imidazole to stabalize charged His, but doesn't actually take the His proton

What is the role of His in the catalytic triad?

H+ acceptor to serine and water increasing it's oxygens Nu: towards the carbonyl

H+ donor to tetrahedral intermediate to yield product

Hydrogen bond donor to intermediate to yield free amine component

Acid-Base catalysis

How does destabalization facilitate catalysis?

Energy of substrate is brought closer to transition state energy and the stress is then relieved at the transition state

Destabalization by desolvation is a method of catalytic substrate destabalization, how does it work?

Remove a very polar functional group from water raising its energy and making it more reactive

Chymotrypsin utilizes 3 catalytic strategies, what are they?

Nu: catalysis, stabilization of the transition state, general acid/base

Why do we observe 2 phases in chymotypsins action?

The first step is faster due to covalent binding of ES intermediate while the second step is slower since it's hydrolysis

What is stage 1 of chymotrypsin cleavage?

Substrate binding --> Nu: attack of serine on the peptide carbonyl --> collapse of the tetrahedral intermediate by protonation of amino group--> Release of amine component

What is stage 2 of chymotrypsin cleavage?

Water binding --> Nu: attack of water on the acyl-enzyme intermediate by His activation general base catalysis--> Collapse of 2nd tetrahedral intermediate --> Release of the carboxylic acid component --> Reprotonation of Set195 by His

What methods of catalysis does Carbonic anhydrase use?

Electrophilic, metal ion

What is the difference between random and ordered sequential mechanism's initial binding?

Random: Either substrate or coenzyme can bind first to enzyme before catalysis
Ordered: Coenzyme must bind before substrate can and then subsequent catalysis

What is the difference between random and ordered sequential mechanism's product release?

Random: Either product or coenzyme can be released first
Ordered: Product must be released before coenzyme

What is the defining characteristic of a double–displacement (ping–pong) reaction?

The existence of a temperature modified substituted enzyme intermediate

What is the general mechanism of a ping–pong reaction?

First substrate binding ––> First product release, Second Substrate binding ––> Second product Release

The difference in free energy between substrate and transition state is indirectly proportional to _______

The concentration of the transition state!

The smaller the diff. in free energy, the greater concentration of transition state

What feature of an enzyme allows for the destabilization of substrate?

An enzyme pocket complementary to the rxn transition state

How does an enzyme compensate for the energy required to destabilize a substrate?

The binding energy compensates

What happens to the activation energy if the enzyme is complementary to the substrate?

The ES complex is more stable and has less free energy in the ground state than the substrate does alone leading to an increase in activation energy

What are the 6 catalytic mechanisms of enzymes discussed in lecture?

1) Proximity and Orientation Effects
2) Preferential binding of the transition state complex
3) Catalysis by destabilizing the substrate
4) Acid–base catalysis
5) Covalent (Electrophilic of Nu:) catalysis
6) Metal Ion catalysis

What side chains are commonly used in acid–base catalysis and what feature of their pK allows this?

1) Asp
2) Glu
3) His
4) Cys
5) Tyr
6) Lys All have pK's in the physiological range

What AA's commonly act as Nu:?

1) Imidazole group of His
2) Unprotonated amino group of Lys
3) Thiol of Cys
4) Carboxyl of Asp
5) Hydroxyl of Ser

What are common cofactors?

1) Fe 2+ and 3+
2) Cu 2+
3) Mn 2+
4) Co 2+
5) Mg 2+
6) Zn 2+

What are common electrophiles?

Carbon atom of a carbonyl
Protonated Imine carbon
Phosphorous of a phosphate group

What type of catalytic mechanism does Complex III use and why is it characterized like that?

Proximity and Orientation effects

Its preorients cytochrome C and subunit cytochrome C1 of complex III for heme–to–heme e– transfer

What type of catalytic mechanism does the catalytic triad of serine protease use and why is it characterized like that?

Catalysis by preferential binding of the transition state because Ser195's Nu: attach on the scissile peptide carbonyl leads to stronger binding by filling the oxyanion hole and hydrogen bonding between backbone NH and CO of Gly193 which it was unable to do prior to its transition state

What are the 3 types of substrate destabilization and what do they all have in common

1) Entropy reduction
2) Desolvation
3) Stress
Destabilization raises the free energy of the substrate bringing it closer to the transition state

Describe how an enzyme can contribute to entropy reduction as a method of substrate destabilization

When Substrate binds enzyme, there are reduced degrees of freedom available for translational motion leaded to a more ordered lower entropy situation
This increases its free energy ––> more reactive

Describe how an enzyme can contribute to desolvation as a method of substrate destabilization

The substrate can only bind without it's polar solvation shell to the enzyme which raises it's energy and makes it more reactive

What types of "stress" can destabilize a substrate and aid in catalysis?

Electrostatic or steric
Similar charged in proximity raises the free enrgy making it more reactive

What's the difference between specific and general acid–base catalysis?

Specific involves the diffusion of H+ or OH– into the catalytic center
General involves acids other than H+ and bases other than OH–

in what ways can a metal ion aid in electrophilic catalysis?

1) Can increase susceptibility to Nu: attach by making it more electron withdrawn
2) By making the leaving group a weaker base aka stabilizing LG's charges
3) By increasing Nu: of water by facilitating leaving of proton and just leaving a metal–bound OH

How can metal ion cofactors aid in catalysis?

1) To shield of stabilize negative charges
2) To mediate Redox through changes in the oxidation state
3) To bind and orient substrates

How does a zymogen regulate chymotrypsins activity?

Chymotrypsin is synthesized as 1 polypeptide chain called chymotrypsinogen which is cleaved and activated by zymogen

How is the zymogen that regulates chymotrypsin regulated?

Trypsinogen is cleaved and activated to trypsin which leads to a protease cascade eventually cleaving and activating chymotrypsin

How does Dicoumoral inhibit proper prothrombin synthesis?

Dicoumoral is a vitamin K antagonist like warfarin.

Vitamin K is essential to proper synthesis, so it's inhibition leads to abnormal prothrombin that cannot bind calcium ion

What is the role of proteolytic cleavage in the formation of a blood clot?

Prothrombin must be proteolytiaclly cleaved to thrombin which cleaves fibrinogen to fibrin which polymerizes with fibrinopeptides which becomes a clot!

How does fibrin polymerize to form a clot?

Glutamate residues on one chain react with lysine residues on another and their formation is catalyzed by transglutaminase

What is the binding scheme and function of Zinc ion in carbonic anhydrase catalysis?

Zn2+ is always bound to 4 ligands, 3 His and 1 H2O

The Zn2+ allows water to lose a proton at neutral pH, making it a stronger Nu: to attack CO2

Describe the Carbonic Anhydrase mechanism

1) Zinc ion facilitates formation of OH from H2O, H+ is taken by proton shuttle

2) CO2 binds active site and is Nu: attacked by Zn2+ bound OH converting CO2 to HCO3- ion

3) Displacement of HCO3- by H2O and regeneration of active site

What is the function of His 64 in carbonic anhydrase catalysis?

His 64 shuttles protons form water to the surface of the protein to be picked up by the buffer

What happens if we're missing a bufffer in carbonic anhydrase?

Without a buffer the Kcat becomes limited to proton diffusion and slows down dramatically

What are the roles of His96, His119, and His94 in Carbonic Anhydrase catalysis

Binding site for Zinc Ion

What methods of catalysis do restriction enzymes use?

1) Electrophilic catalysis

2) Metal ion catalysis

3) Substrate distortion

What are Type II restriction enzymes used for?

Cloning and Sequencing DNA

They generate a 3' OH and 5' phosphate

What is the cofactor for Type II restriction enzymes and what is it's purpose


1) Distorts the substrate (Kink the TA DNA pairs)

2) Increases Nu: of water

How does magnesium contribute to Type II restriction enzyme specificity?

Only cognate sequence bind to and are distorted by Mg2+

Distortion of cognate complexes is offset by the increased binding energy associated with the Mg2+ - DNA complex.

Noncognate sequences cannot achieve full binding energy and so distortion is not offset

How does water hydrolyze a cognate DNA sequence?

In-line single displacement

Activated water attacks phosphorous as a Nu: and leads to inversion of stereochem via a pentacoordinate intermediate

Where do a Myosin get its energy for conformational chagnes?

Hydrolysis of Mg2+ - ATP complex

What catalytic mechanism does ATP hydrolysis utilize?

General Acid/Base

What is the function of Mg2+ in ATP hydrolysis?

ATP:Mg2+ is the substrate

Mg2+ is not a component of the active site

Mg2+ increases susceptibility of bond cleavage by withdrawing electron density

What about ATP hydrolysis is unique in the Myosin active site?

ATP hydrolysis is freely reversible, thus each ATP is cleaved and reformed several times before the products are released

What is the mechanism that enables Myosin to change conformation?

1) Hydroxide is formed from water through deprotonation by Ser 236, and the resulting OH- attacks the gamma-phosphoryl group --> This causes the ether bonds to break between the beta and gamma phosphoryl

2) Ser 236 is then deprotonated by the Gamma-phophoryl oxygen

What is the P loop?

Characteristic loop between first beta strand and first helix of the NTP-binding core that interacts with phosphoryl groups on the bound nucleotide