Week 6: M-M Inhibitors, Allosteric Enzymes, & Control of Activity Flashcards
(131 cards)
1
Q
Mixed noncompetitive inhibition is similar to noncompetitive inhibition but binding of inhibitor DOES affect _________
and still lowers ______
A
binding of substrate and vice versa
Vmax
2
Q
Similar to a Lineweaver-Burk plot for a noncompetitive inhibitor, one for a mixed noncompetitive inhibitor:
_____ and _______ change
however, _______ changes from that of noncompetitive because _______
A
slope, y-intercept
x-intercept because -1/KM becomes a smaller negative value
3
Q
Mixed competitive inhibition:
______ decreases
_______ increases (or decreases)
A
Vmax
KM
4
Q
With pure noncompetitive inhibition, the binding of the inhibitor does not change __________ at all and vice versa; thus the _______ does not change. With mixed inhibition, the _______ such that the ______ for the substrate is ______ in the presence of inhibitor.
A
affinity of the enzyme for substrate, KM
substrate and inhibitor do affect each other, KM
different
5
Q
In uncompetitive inhibition, inhibitor can only bind to the _______, never the _______
A
ES complex
free enzyme
6
Q
In uncompetitive inhibition, ______ decreases because it causes a ______ of product formation.
KM _______ because Le Chatliers Principle: as ______ formed, formation of more ______ favored.
However, because ______ decreases remember it still lowers enzyme activity.
A
Vmax, lower rate
decreases, EIS, ES
Vmax
7
Q
Lineweaver-Burk equation:
A
1/V = KM/Vmax x 1/[S] + 1/Vmax
8
Q
Lineweaver-Burk plot for uncompetitive plot contains ________ meaning ______ slope, ______ intercepts
Vmax and KM _______ to same extent
A
parallel lines
same slope
different intercepts
decrease
9
Q
Lineweaver-Burk equation for uncompetitive inhibition:
A
1/V = a’KM/a’Vmax x 1/[S] + a’/Vmax
1/V = KM/Vmax x 1/[S] + a’/Vmax
10
Q
Irreversible inhibition is _______ binding of inhibitor to enzyme, causing _______ inactivation
A
covalent
permanent
11
Q
Suicide substrates: Molecules bind to enzyme irreversibly and ______ it, reaction can’t move ________ and can’t ________ either
also called _______ substrates
A
inactivate, through the reaction sequence, reverse it
Trojan horse (sneak in)
12
Q
Allosteric enzymes can be controlled by many different mechanisms, including inhibition and activation by ________.
A
reversibly binding molecules
13
Q
_________ is a common way to regulate an allosteric enzyme that is part of a complicated pathway.
A
Feedback inhibition
14
Q
What features distinguish enzymes that undergo allosteric control from those that obey the Michaelis–Menten equation?
Allosteric enzymes display ________ kinetics when rates are plotted versus substrate concentration. Michaelis–Menten enzymes exhibit _______ kinetics. Allosteric enzymes usually have _________, and the binding of substrates or effector molecules to one subunit __________.
A
sigmoidal
hyperbolic
multiple subunits
changes the binding behavior of the other subunits.
15
Q
ATP acts as a _______ of ATCase, and CTP acts as ________.
A
positive effector
an inhibitor
16
Q
_____ acts as a positive effector of ATCase, and _____ acts as an inhibitor.
A
ATP, CTP
17
Q
The sigmoidal curve of the plot of reaction rate against substrate concentration reflects the _________ of allosteric enzymes
A
cooperative behavior
Enzymes that exhibit cooperativity do not show hyperbolic curves of rate versus substrate concentration. Their curves are sigmoidal. The level of cooperativity can be seen by the shape of the sigmoidal curve.
18
Q
Inhibitors make the shape of the curve ______ sigmoidal, thus ______ cooperative
A
more, more
19
Q
Activators make the shape of the curve _____ sigmoidal, thus _____ cooperative
A
less, less
20
Q
Allosteric proteins (including enzymes) are ones in which ________ at one site affect the _______
* Most common in proteins with _________
* Can have positive or negative _______
A
subtle changes
structure and function at another site
quaternary structure
positive or negative cooperativity
21
Q
Structural organization of enzyme ATCase:
A
2 catalytic trimers + 3 regulatory dimers
22
Q
Regulatory subunits are where the ________
A
allosteric effectors bind (inhibitors and activators)
23
Q
Catalysis occurs in absence of ________
* No ______ in that case
A
R subunits
regulation
24
Q
Why is ATCase not considered a “competitive” inhibitor even though for both this and competitive inhibitors, Vmax stays constant?
A
Doesn’t follow lock-and-key induced fit and M-M kinetics hyperbolic plot associated with “competitive” inhibitor (instead sigmoidal)
25
K systems:
Inhibitors/activators change K values (substrate affinity)
26
K0.5:
Substrate level at ½ Vmax in a K system
* Analogous to KM for nonallosteric enzymes
27
V systems:
Inhibitors/activators that change Vmax
28
Allosteric effector: ______, _______, or ________
that binds to _______ enzyme and affects activity
Substrate, inhibitor, activator
allosteric
29
Homotropic effects: Occur when several ______
molecules are bound
* Ex:
identical
Binding of aspartate to ATCase
30
Heterotropic effects: Occur when _____
substances are bound
* Ex:
different
Activation of ATCase by ATP when substrate also bound
31
Michaelis-Menten enzyme never involves product ______ and product production kinetics follows a ______ saturating V vs. [S] curve.
feedback activation
hyperbolic
32
ATP, a purine nucleotide, is a _______ of ATCase. This ______ action of ATP is thought to be due to the cell's need to keep ________ approximately balanced.
positive regulator
positive feedback
purine and pyrimidine nucleotide levels
33
A K system is an ______ enzyme for which the _______ of the enzyme for its substrate is altered in the presence of effector and for which the apparent ______ does not change.
allosteric, apparent affinity
Vmax
34
Both _______ cooperativity cause the V vs. [S] plot to deviate from the ______ plot of a Michaelis-Menten enzyme.
The ________ is reflected in the extent of curvature of the V vs. [S] plot.
positive and negative
hyperbolic
degree of cooperativity
35
Triaclyglycerols are typically used for the ______; they do not appear in ______ of animals. They are mostly deposited in _______ and are also found in the ______ in the form of very low density lipoprotein (VLDL) and chylomicrons.
storage of fatty acids
cell membranes
adipose tissue
blood
36
Waxes are found on the ______ of leaves.
Waxes frequently form ______ for plants as well as animals.
outside
protective coatings
37
In concerted model, all enzyme subunits are in the _____ form, either R or T. Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeaux proposed this model.
same
38
In sequential model, enzyme subunits can be ________ independent of each other.
in either the R or the T form
39
What property of a metal ion makes it a useful cofactor in enzyme-mediated catalysis?
A metal ion can act as a Lewis acid.
A metal with an excess complement of electrons can readily donate a lone pair of electrons, forming a metal ion. Metal ions are electron deficient and can act as Lewis acids, accepting electrons into unoccupied d-orbitals to form metal complexes.
The donation of electrons from a Lewis base (the substrate in the case of enzyme-mediated catalysis) can cause electronic strain on other bonds in the substrate, weakening them and making them easier to break.
40
R:X + Z: --> R:Z + X:
SN1 reactions are _______ in nature. In the illustrated reaction, R:X is the molecule that breaks down to control the rate of the reaction. Only later does X: react with Z:. Thus, this reaction will have a first order rate constant and its rate will depend on [R:X].
SN2 reactions are ______ in nature. In the illustrated reaction, R:X will react with Z: initially to form R:Z. Thus, this reaction will have a second order rate constant and its rate will depend on both [R:X] and [Z:].
unimolecular
bimolecular
41
Lipids can be grouped based on:
having a preponderance of ______ groups.
their _______ in nonpolar solvents.
nonpolar
high solubility
42
A K system is an ______ enzyme in which the binding of inhibitor alters the apparent _______ needed to reach one-half Vmax, S0.5.
allosteric, substrate concentration
43
A V system is an allosteric enzyme in which the binding of inhibitor changes the _____ of the enzyme but not the _____ .
Vmax, S0.5
44
S0.5 is the substrate concentration that leads to _____ the maximal velocity. This term is used with _____ enzymes, where the term _____ is not appropriate.
half of
allosteric
KM
45
In the concerted model for allosteric behavior, the binding of substrate, inhibitor, or activator to one subunit ________ between an active form of the enzyme, which binds substrate strongly, and an inactive form, which does not bind substrate strongly.
shifts the equilibrium
46
In the sequential model, the binding of substrate induces the __________ in one subunit, and the change is ______ along to other subunits.
conformational change
subsequently passed
47
Allosteric enzymes tend to be enzymes with ______ structure
quaternary
48
Since the T form is much _____ to bind substrate, its dissociation constant ([E][S]/[ES]) would be _____
less likely
very large
49
Enzyme mostly in ______ in the absence of substrate
T form
50
In concerted model, change from T to R (conformations) change _______.
Protein has two conformations:
* Active R (relaxed) - Binds substrate with ______
* Inactive T (tight or taut) - Binds substrate with _______
simultaneously
high affinity
lower affinity
51
L =
equilibrium ratio of T:R
[T] >> [R]
52
c =
ratio of KR:KT
53
Presence of substrate shifts equilibrium from _______ to _____
* Driven by LeChâtlier’s principle
* Substrate binds ______
T (inactive)
R (active) form
R form
54
Higher L means higher favorability of ______ and ______ sigmoidicity
free T form (since L = T/R)
greater
55
Lower c means higher affinity of ______, meaning ______ sigmoidicity
R form for S
greater
56
Higher c means _____ sigmoidicity
less
57
Binding of activator (A) shifts equilibrium to favor ____
* Less need for _____
* Curve ______ sigmoidal (________- cooperativity)
R
S to shift to R form
less sigmoidal (reduced cooperativity)
58
Binding of inhibitor (I) shifts equilibrium to favor ____
* ______ need for S to shift to R form
* Curve _____ sigmoidal (______ cooperativity)
T
Greater
more
increased
59
When c = 0, ____ is infinite because the substrate ______. Cooperativity in this case is ______.
As c increases, it means the difference in binding for T and R ______. We see line become ______ sigmoidal as the need for cooperativity ______.
KT is infinite
does not bind to KT
high (once some substrate has bound, more is likely to)
decreases
less
drops
60
In sequential model, binding of ____ induces ______ from T to R form
S
conformational change
61
In sequential model, substrate binds ____ and changes to ______,
induces same change to ______, binds substrate with higher _____
T form
R form
adjacent subunit
affinity
62
Sequential Model
* Cooperative binding of S to allosteric enzyme
* _____ is favored by allosteric activator
* Allosteric inhibitor binds ____
* Conformational change to S binding site
* Allosteric inhibition occurs by induced-fit mechanism
R form
T form
63
Sequential model has a unique feature: Negative cooperativity -->
Negative cooperativity: Binding of first ligand results in lower affinity for next
64
In the concerted model, all the subunits in an allosteric enzyme are found _____. They are in equilibrium, with each enzyme having a characteristic ratio of the T/R. In the sequential model, the subunits _____.
the same form, either the T form or the R form
change individually from T to R
65
The _____ model can explain negative cooperativity, because a substrate binding to the T form could induce other subunits to switch to the T form, thereby reducing ______.
sequential
binding affinity
66
The L value is the ______ ratio of the ____. The c value is the ratio of the _______ for substrate and the two forms of enzyme, such that _____.
equilibrium, T/R form
dissociation constants
c = KR/KT
67
Phosphorylation is the _____ attachment of a _____ group to an amino acid ______
covalent
phosphoryl
side chain
68
control of enzyme activity through phosphorylation: usually phosphorylated on ______ groups of ________
hydroxyl
Ser, Thr, Tyr
69
Phosphoryl group usually comes from _____
ATP
70
_____ add phosphoryl groups and ______ take them off
Kinases
phosphatases
71
Glycogen phosphorylase:
Phosphorylase _____ more
active than ______
* Two forms (a & b) respond
to different ______
a, b form
allosteric
effectors
72
A kinase is an ______ that ______ a protein using a high-energy phosphate, such as _______, as the phosphate donor.
enzyme
phosphorylates
ATP
73
______ are the three most often phosphorylated amino acids in proteins that are acted upon by kinases. ______ is another one that is often phosphorylated.
Serine, threonine, and tyrosine
Aspartate
74
Glycogen phosphorylase is controlled allosterically by several molecules. In the muscle, ______ is an allosteric activator. In the liver, ______ is an allosteric inhibitor. Glycogen phosphorylase also exists in a phosphorylated form and an unphosphorylated form, with the _________ being more active.
AMP, glucose
phosphorylated form
75
Inactive nascent proteins are called _____:
Enzymes ____ and ready to go when _____, this contributes to an amplifying effect to give large effect in ________
zymogens
pre-formed, activated
small amount of time (faster responses)
76
General structure of chymotrypsinogen:
cross-linked by disulfide bonds
77
Chymotrypsinogen is first cleaved by _____ to give one active form, cleaves itself to give most ______
Part of _____ removed, which alters ______ to give _____
trypsin
most active form
primary structure
tertiary structure
active form
78
Why is it necessary or advantageous for the body to make zymogens?
Zymogens are often seen with ______ that are produced in one tissue and used in another. If the enzyme were active immediately upon production, it would _____, where it would cause _____. By having it produced as a zymogen, it can be ______ to the digestive tissue, such as the stomach or small intestine, where it can then be activated.
digestive enzymes
digest other cell proteins
great damage
safely made and then transported
79
Nature of active site. For each enzyme you would have to consider:
which amino acid side chains (residues) are present
spatial relationship of essential amino acids in active site
chemical mechanism in which essential amino acid residues catalyze the reaction
80
General reaction of chymotrypsin:
_____ substrate
Can use _______
Two phases:
natural
p-Nitrophenyl acetate
p-nitrophenyl acetate hydrolyzed by chymotrypsin in two stages:
* Initial burst
* Formation of covalent intermediate, rapid
* Slower phase
* Hydrolysis
* Release of acetate
81
3 residues of the catalytic triad:
Ser, His, Asp
Folding of backbone positions essential amino acid residues around active-site pocket
82
Enzymes that catalyze biochemical reactions have been formally classified into ______ subgroups according to reaction type.
six
83
6 classes of enzymes:
Oxidoreductase
Transferase
Hydrolase
Lyase
Ligase
Ismoerase
84
Oxidoreductase
facilitates redox reactions
85
Transferase
catalyze the transfer or exchange of certain groups
86
Hydrolase
adding water to break bonds
87
Lyase
breaking or making bonds
88
Isomerase
moving the order of attachment
A-B-C --> A-C-B
89
Ligase
ATP hydrolyzed to release energy
90
Many enzymes require _____ for activity
cofactors
91
Cofactors:
Coenzymes:
coenzymes, metal ions
prosthetic group, cosubstrate
92
NAD+ is an example of a ______
Participate in _____ reactions
cosubstrate
redox
93
Structural components of NAD+?
Nicotinamide ring, adenine ring, two sugar-phosphates
94
Where prosthetic groups are ______ to enzyme, cosubstrates can _______
bound
enter or leave active site
95
apoenzyme
before cofactor added, not functional
96
B6 vitamins participate in amino acid ______
biosynthesis
97
_______ are the two most critical amino acids in the active site of chymotrypsin.
Serine and histidine
98
Why does the enzyme reaction for chymotrypsin proceed in two phases?
The initial phase releases the _____ and involves an _____ intermediate. This step is _____ than the second part, in which _____ comes into the active site and breaks the______ bond.
first product, acylenzyme
faster
water, acyl–enzyme
99
Briefly describe the role of nucleophilic catalysis in the mechanism of the chymotrypsin reaction.
In the first step of the reaction, the _____ is the nucleophile that attacks the substrate peptide bond. In the second step, ______ is the nucleophile that attacks the acyl-enzyme intermediate.
serine hydroxyl
water
100
Explain the function of histidine 57 in the mechanism of chymotrypsin.
Histidine 57 performs a series of steps involving general base catalysis followed by general acid catalysis. In the first phase, it takes a hydrogen from serine 195 , acting as a general base. This is followed immediately by an acid catalysis step, in which it gives the hydrogen to the amide group of the peptide bond that is breaking. A similar scheme takes place in the second phase of the reaction.
101
Explain why the second phase of the chymotrypsin mechanism is slower than the first phase.
The first phase is faster for several reasons. The serine at position 195 is a strong nucleophile for the initial nucleophilic attack. It then forms an acyl-enzyme intermediate. In the second phase, water is the nucleophile, and it takes time for water to diffuse to the right spot to perform its nucleophilic attack. It is also not as strong a nucleophile as the serine. Therefore, it takes longer for water to perform its nucleophilic attack and break the acyl-enzyme intermediate than it takes for serine to create it.
102
Explain how the pKa for histidine 57 is important to its role in the mechanism of chymotrypsin action.
Histidine 57 exists in both the protonated and unprotonated form during the chymotrypsin reaction. Its pKa of 6.0 makes this possible in the physiological pH range.
103
Common organic reaction mechanisms, such as ______ and ______, are known to play roles in enzymatic catalysis
nucleophilic substitution
general acid–base catalysis
104
In biochemistry mechanisms, what group is often attacked by a nucleopile?
The carbon of a carbonyl group is often attacked by a nucleophile.
105
General acid catalysis is the part of an enzyme mechanism in which an amino acid or other molecule donates a _______ to another molecule.
hydrogen ion
106
Absolute specificity – Catalyzes reaction of ______ to specific product
one unique substrate
107
Relative specificity – Catalyzes reaction of _______ to give structurally related products
structurally related substrates
108
Stereospecificity –
Suggests ______ binding
One stereoisomer reacted or
formed in preference to all others
asymmetric binding
109
Nature of transition state is ______
between substrate and product
* ______ from either substrate or product
intermediate in structure
Different shape
110
Transition-state analog: Synthesized compounds
that ______ of transition state
mimic form
111
Abzymes:
Antibodies with ______
Raised in response to ______
catalytic activity
transition state analogues
112
What is the relationship between a transition-state analog and the induced-fit model of enzyme kinetics?
The induced-fit model assumes that the enzyme and substrate must both move and change to conform to each other perfectly. Thus, the true fit is not between the enzyme and substrate but between the enzyme and the transition state of the substrate on its way to product. A transition-state analogue fits the enzyme nicely in this model
113
Explain how a researcher makes an abzyme. What is the purpose of an abzyme?
An abzyme is created by injecting a host animal with a transition-state analogue of a reaction of interest. The host animal makes antibodies to the foreign molecule, and these antibodies have specific binding points that mimic an enzyme surrounding a transition state. The purpose is to create an antibody with catalytic activity.
114
Most coenzymes are derivatives of compounds we call _____.
vitamins
For example, nicotinamide adenine dinucleotide is produced from the B vitamin niacin. Flavin adenine dinucleotide comes from riboflavin.
115
Proteins, nucleic acids, and carbohydrates are grouped by common structural features found within their group. What is the basis for grouping substances as lipids?
Solubility properties (insoluble in aqueous or polar solvents, soluble in nonpolar solvents). Some lipids are not at all structurally related.
116
An allosteric enzyme will feature a ______ curve that represents _____, the changes that occur in the binding
activity of an enzyme in response to the binding of a ligand / substrate. This is possible because of the ______
present on the enzyme that will allow for regulation and multiple active sites.
Michaelis-Menten enzymes will always have a ______ curve because they are ______ structure proteins; they only
have one subunit that can bind one ligand at a time. While they do have sites for inhibitors to bind, they do not have
allosteric effectors that can alter binding patterns.
sigmoidal
cooperativity
multiple subunits
hyperbolic
tertiary
117
The concerted model is an ‘all-or-nothing’ model that has substrates bind to the ______ of the enzyme. The equilibrium of
R/T form is determined by LeChatlier’s principle, where the presence of substrate will shift the enzyme to have all of its
subunits to be _____ where it can bind. This equilibrium is also affected by the presence of activators / inhibitors that can
‘override’ the presence / absence of substrate. Most molecules exist in the _____ when substrate is absent, which is also
explained by two equilibrium constants:
R form, R form
T form
L: Ratio of T state / R state. This is high in the concerted model (more T state)
C: Kr/Kt (dissociation constants). This value is low in the concerted model (more T state as Kr << Kt)
118
The sequential model, on the other hand, has substrates bind to the ______ of the enzyme. This binding to the _______ will
shift the bound subunit to the _____ along with the ______, indicating that conformational changes happen ______, not all at once. Inhibitors will bind to the T form of the enzyme and induce conformational changes in adjacent
subunits to lower _______. The sequential model has the unique property of also allowing for the binding of one ligand to
______ the affinity of binding for the next one. This is called ________, which can only be explained by the
sequential model; the concerted model does not allow for such a feature
T form, T form
R form
adjacent subunit
one at a time, not all at once
affinity
reduce
negative cooperativity
119
The T (taut) form is the conformation of the enzyme that has ______ affinity for the substrate and will therefore catalyze
______ (but not zero, as we see with the sequential model). The R (relaxed) form is the conformation in which the
enzyme has ______ affinity for its substrate and will bind it with ease to catalyze _______.
very low, few reactions
much higher, many reactions
120
An enzyme is a ______ protein
catalytic
121
An apoenzyme is the ______ form of a complete enzyme that just needs its ______ present so that it can become a
holoenzyme. For example, hexokinase in glycolysis is a fully formed protein, but it needs a _____ in order to
carry out its reaction.
inactive, cofactor
magnesium ion
122
A zymogen is an ______ that requires a modification in ________ in order to be activated. From the slides, we are provided with the example of _______ that undergoes hydrolysis via _____ to yield its pi-form that is then further digested to give its active ______. This is a feature of many _______ enzymes – it is a bad idea to have them be active in the pancreas where they are synthesized; let them do their work in the small intestine where the food is!
inactive protein
primary structure
chymotrypsinogen, trypsin
alpha form
digestive
123
If K is the dissociation constant, would KR or KT be expected to be higher? Why?
We expect KT to be higher since this is a dissociation constant; the T form of the enzyme has much lower affinity for
substrate, so it is less likely to bind it and will therefore be more favored in equilibrium.
124
How would you expect the “L” value for an allosteric enzyme to change in the presence of an inhibitor?
Given that L is the ratio of T/R form, an inhibitor will shift the equilibrium to favor the T state and therefore increase L.
On the slides, you can see that the curve shifts to the right when L increases; this is MORE cooperativity.
125
Consider an equilibrium between the T and R form of an allosteric enzyme. As the R form binds substrate to
form the enzyme-substrate complex, what happens to the equilibrium? How does this explain allostery for this
system?
This all comes down to LeChatlier’s principle (again). Recall that FREE enzymes have an equilibrium between the T/R
state. When a substrate binds to an R state enzyme and forms [ES], the concentration of free R state enzyme is effectively
decreased, so the system needs to shift towards the R state in order to replenish the free R state enzymes. This explains
allosteric effects as the binding of substrate is initially slow (less substrate = less binding of substrate to form [ES] and
shift the equilibrium) but once the substrate concentration increases to an appreciable amount, the equilibrium will begin
to quickly shift away from the T state.
126
Hydrolase: Catalyze reactions in which bonds are cleaved by adding _____.
Lyases: Catalyze reactions in which groups (H2O, CO2, NH3, etc) are _____
water
removed to form a double bond or are added to a double bond
127
Answer these questions about the chymotrypsin mechanism:
a. Which amino acid of the catalytic triad acts as a nucleophile to attack a carbon on the substrate?
b. What role does aspartate play in the mechanism?
a. Serine
b. Donates hydrogen bonds to histidine to provide stability as it shifts between acidic/basic forms.
128
Chymotrypsin mechanism:
The bond cleavage always occurs at the ______ side of one of these three residues:
Explain how the active site orients the peptide such that the cleavage always occurs on this side.
Bonus: explain how the oxyanion is stabilized in the oxyanion hole.
C-terminus
Tyrosine, Phenylalanine, or Tryptophan.
Hydrophobic pocket
Ser-195 and Gly-193 provide hydrogen bonds (donated) to the oxyanion to stabilize it.
129
d. There are two tetrahedral intermediates. Why are they called this?
They are formed from nucleophilic attacks that take place on the carbonyl carbon and force the formation of an oxyanion.
Because they are unstable, they do not last long and usually result in the cleavage of another carbon-oxygen bond to restore the carbonyl form.
130
e. The acyl-enzyme intermediate is formed after the peptide bond cleavage. Why is it important that the reaction continues? i.e., why can’t it stop here now that it has cleaved the peptide?
In order to perform another reaction, the enzyme’s original state must be achieved; as of now, it is not capable of performing another reaction. The primary goal is restoring serine to its hydroxyl form instead of being involved in
an ester bond.
131
f. What molecule must enter the active site to continue the reaction after the acyl-enzyme is formed?
i. Does this molecule act as an acid or a base?
ii. In what other way does this molecule react?
i. Water must enter the active site. It will act as an acid and donate a proton to histidine to form a hydroxide ion.
ii. The hydroxide ion that is formed will be a strong nucleophile that attacks the carbonyl carbon on the acyl-enzyme molecule and form another tetrahedral intermediate that breaks down to release the serine and restore the enzyme to its
original state
