Binding and recognition of substrates and basis of chemical and enzymatic catalysis Flashcards
1
Q
The function of most proteins involve:
A
- the ability to recognize and bind to other molecules
- involves same non-covalent interactions as protein folding
2
Q
How are other molecules recognized
A
- non polar patches on surface of target by hydrophobic effect
- match shapse to maximize close contact (van der waals effect)
- match of charged group of H-bond donors and acceptors
3
Q
What is the role of quaternanry strucute in protein-protein intereactions
A
- quaternanry strucute recognize and bind thier parter proteins
- EX: enzymes recognize and bind thier specific target protein and catalyse them
- EX: anti bodies bind and identify foreighn molecules
4
Q
How does chymotrypsin bind to polypeptides
A
- recognize Phe, Tyr, Trp because of aromatic group
- “groove” in chymotrypsin binds a peptide chain by H-bonds to backbone
- side chain bindind pocket is large and surrounded by non-polar amino acids (these aa are non polar also)
- note related enzymes trypsin and alastase are similar to chymotrypsin except for side chain binding pockets (tryp binds to Lys and Arg while elastase bidns to Ala, and Gly)
5
Q
The target of the enzyme is called its ____
A
substrate
6
Q
How do enzymes speed up reactions?
A
Rate = pZe^(- Ea/RT)
Z= is the collision frequency
- p is the probability factor, probability that collision leads to reaction- realated to rate of reactants, related to orientation of reactants
- Ea= activation energy, must be put into a reaction in initial steps, break or distort bonds
7
Q
How much does an enzyme speed up a chemical reaction?
A
10^6-10^17 (typically 10^10) times faster
8
Q
Why are uncatalyzed reactions slow?
A
- without catalyst reactions depend on random events
- molecules must collide
- they must be in the right orientation
reacting molecules require a threshold energy
- if these conditions reaction MAY occur, but depends on chance
9
Q
What is the proximity effect
A
- How do enzymes eliminate the randomness of collisions
- random motion of molecules leads to close encounters but few hits between reacting pairs
- enzyme binds substrates in a special pocket known as the active site, holds them close together long enugh for rxn to proceed
10
Q
What is the orientation effect
A
- How enzymes hold substrates in the correct orientation
- two molecules may meet by random collision, but reactive groups may not be properly lined up for reaction
- enzyme binds substrates, holding them in active site so reactive groups are ideally sligned
- this is the orientation effect (inc p)
11
Q
How are proximity and orientation related to enzymes
A
- enzymes eliminate randomness for the rxn, this randomness is related to entropy
- must have good proximity between substrate and reactive group
- ideal alignment of substrate and reactive group
12
Q
How do enzymes decrease EA
A
- proximity and orientation are physical effects that speed up enzyme reactions
- enzymes use chemical catalysis to speed reaction by lowering EA
- Ea can be lowered by finding a better chemical pathway
- enzymes must spped reactions at neutral pH and normal temperature
13
Q
What is nucleophilic catalysis
A
- enzymes can speed up reactions by providiing a better nucleophile (lone pair of electrons availbale to share)
- reaction occurs between protein and enzyme not protein and water
- note these enzymes are proteins, better nucleophiles are (Cys-SH, His- N, Asp or Gly -COO, and rarely tyr or ser OH or LysNH2)
14
Q
What is electrophilic catalysis
A
- an electrophile= electron seeking group
- are no really good electrophilic amino acids
- enzyme may contain a non-amino acid helper molecule called a prosthetic group
ex: pyridoxal phosphate (cofactor or coenzyme) with electrophilic aldehyde group - binds at enzyme cataytic site, initiates reaction by withdrawing electrons from substrate
15
Q
What is general acid and base catalysis?
A
- General acid: catalysis by an amino acid side chain that donates H+
- General base: catalysis by an amino acid aide chain that removes H+
- H+ excahnge takes place right at the site of reaction, so pH of surroundings is not affected
- Gain or loss of one H+ in a small confined volume can have same effect as strong acid or base
- drastically changes catalytic site, even if one proton donated.accepted it can have effect of very strong acid because in very small volume
16
Q
How is the transition state stabilized
A
- reactions must pass through transition state to proceed, key atoms may change shape (bond may stretch)
- enzyme can help by binding the substrate in the ideal shape for the transition state
- binding pocket is in size/angle/shape needded for transition, when it binds it will stretch or change shape of bond to fit properly
- less activation energy is needed is the enzyme active site is complementray to the transition state
