Name: Nguyễn Tấn Phú

ID: BTBCIU16057
Question 1: How enzymes are categorized into different classes and types?
Enzymes are the catalysts of metabolism, allowing living systems to achieve kinetic control over the
thermodynamic potential within organic reactions. Enzymes have three distinctive attributes that are
essential to their biological purpose: enormous catalytic power, great selectivity in catalyzing only very
specific reactions, and the ability to be regulated so that their activity is compatible with the momentary
needs of the cell
Enzymes are classified according to the type of reaction they catalyze, so enzymes are divided into six
functional classes. Besides, many enzymes have been named by adding the suffix “-ase” to the name of
their substrate or to a word or phrase describing their activity. Other enzymes were named by their
discoverers for a broad function, before the specific reaction catalyzed was known. Enzymes may be
simple proteins or they may be proteins complexed with nonprotein components called cofactors.
Cofactors include metal ions and organic molecules known as coenzymes [1].
Class no. Class name Type of reaction catalyzed
1 Oxidoreductases Transfer of electrons (hydride ions or
H atoms)
2 Transferases Group transfer reactions

3 Hydrolases Hydrolysis reactions (transfer of

functional groups to water)

4 Lyases Cleavage of C—C, C—O, C—N, or

other bonds by elimination, leaving
double bonds or rings, or addition of
groups to double bonds
5 Isomerases Transfer of groups within molecules
to yield isomeric forms
6 Ligases Formation of C—C, C—S, C—O, and C
—N bonds by condensation reactions
coupled to cleavage of ATP or similar
cofactor
 Translocases also consider as enzyme that catalyzes the movement of ions or molecules across
membranes or their separation within membranes.

Question 2: Elaborating on the nature of the interactions between enzymes and the corresponding
substrates (i.e. what kinds of possible interaction between them).
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The reactant in an enzyme-catalyzed reaction is called the substrate. The fact that graphs of enzyme
activity as a function of substrate concentration show a limiting plateau or saturation level was the
important clue that an enzyme (E) actually binds its substrate (S) to form an enzyme: substrate (ES)
complex that can react to yield product (P). Enzyme must stabilize the transition state complex EX‡,
more than they stabilize the enzyme-substrate complex, ES. Put another way, enzymes are designed by
nature to bind the transition state more tightly than the substrate or product. Enzyme-catalyzed
reactions are typically 107 to 1014 times faster than their uncatalyzed counterparts. The catalytic
mechanisms which contribute to the prowess of enzymes include: entropy loss in ES formation,
destabilization of ES due to strain, desolvation or electrostatic effects, and covalent catalysis, general
acid-base catalysis, metal ion catalysis, and proximity and orientation effects. When a substrate binds to
an enzyme, the (usually large) intrinsic binding energy is compensated by entropy loss and
destabilization in the ES complex, but not in the EX‡ complex. The transition state for any reaction is a
‘moving target’ - atransient species that exists for only 10 -14 – 10-13 s. The short lifetime of the transition
state prevents quantitative studies of this complex, but the dissociation constant for the EX‡ complex
can be estimated to be on the order of 10 -15 M. Transition state analogs are stable molecules that
resemble the transition state for a particular reaction, and that therefore bind very tightly to their
respective enzymes. Since they are only approximations of only approximations of the transition state
structure, transition state analogs cannot, however, bind as tightly as the transition state itself [2].
There are four important types of interaction that hold the substrate in a defined orientation and form
an enzyme-substrate complex (ES complex): hydrogen bonds, van der Waals interactions, hydrophobic
interactions and electrostatic force interactions. Formation of each weak interaction in the ES complex is
accompanied by release of a small amount of free energy that stabilizes the interaction. The energy
derived from enzyme-substrate interaction is called binding energy, delta GB. Its significance extends
beyond a simple stabilization of the enzyme-substrate interaction. Binding energy is a major source of
free energy used by enzymes to lower the activation energies of reactions [2].
There are three proposed models of how enzymes fit their specific substrate: the lock and key model,
the induced fit model, and the conformational selection model. The latter two are not mutually
exclusive: conformational selection can be followed by a change in the enzyme's shape. The specific
action of an enzyme with a single substrate can be explained using a Lock and Key hypothesis.  The
active site and substrate are two stable structures that fit perfectly without any further modification,
just like a key fits into a lock. If one substrate perfectly binds to its active site, the interactions between
them will be strongest, resulting in high catalytic efficiency [3]. The induced fit model is a development of
the lock-and-key model and assumes that an active site is flexible and changes shape until the substrate
is completely bound. The enzyme initially has a conformation that attracts its substrate. Enzyme surface
is flexible and only the correct catalyst can induce interaction leading to catalysis. Conformational
changes may then occur as the substrate is bound. After the reaction products will move away from the
enzyme and the active site returns to its initial shape [4]. Conformational selection hypothesis suggests
that enzymes exist in a variety of conformations, only some of which are capable of binding to a
substrate. When a substrate is bound to the protein, the equilibrium in the conformational ensemble
shifts towards those able to bind ligands [5].
Question 3:  Eplaining why nature decided the nature of the enzyme-substrate interaction

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The noncovalent interactions between enzyme and substrate help stabilize protein structure and
protein-protein interactions. These same interactions are critical to the formation of complexes
between proteins and small molecules, including enzyme substrates. The interaction between substrate
and enzyme in this complex is mediated by the same forces that stabilize protein structure, including
hydrogen bonds and hydrophobic and ionic interactions. Its significance extends beyond a simple
stabilization of the enzyme-substrate interaction. Binding energy is a major source of free energy used
by enzymes to lower the activation energies of reactions- the energy that is required to promote the
formation of transition state intermediate. The three dimensional cleft is formed by the groups that
come from different part of the amino acid sequences. The active site is only a small part of the total
enzyme volume. It enhances the enzyme to bind to substrate and catalysis by many different weak
interactions because of its nonpolar microenvironment. The arrangement of atoms in the active site is
crucial for binding spectificity. The overall result is the acceleration of the reaction process and
increasing the rate of reaction. Furthermore, not only do enzymes contain catalytic abilities, but the
active site also carries the recognition of substrate [1].
The induced-fit model involves the changing of the conformation of the active site to fit the substrate
after binding. Also, in the induced-fit model, it was stated that there are amino acids that aid the correct
substrate to bind to the active site which leads to shaping of the active site to the complementary
shape. Induced fit is the model such that structure of active site of enzyme can be easily changed after
binding of enzyme and substrate. The binding in the active site involves hydrogen bonding, hydrophobic
interactions and temporary covalent bonds. The active site will then stabilize the transition state
intermediate to decrease the activation energy. But the intermediate is most likely unstable, allowing
the enzyme to release the substrate and return to the unbound state .
Properties affect binding:
1. Complementarity: Molecular recognition depends on the tertiary structure of the enzyme which
creates unique microenvironments in the active/binding sites. These specialized
microenvironments contribute to binding site catalysis.
2. Flexibility: Tertiary structure allows proteins to adapt to their ligands (induced fit) and is
essential for the vast diversity of biochemical functions (degrees of flexibility varies by function)
3. Surfaces: Binding sites can be concave, convex, or flat. For small ligands – clefts, pockets, or
cavities. Catalytic sites are often at domain and subunit interfaces.
4. Non-Covalent Forces: Non-covalent forces are also characteristic properties of binding sites.
Such characteristics are: higher than average amounts of exposed hydrophobic surface, (small
molecules – partly concave and hydrophobic), and displacement of water can drive binding
events.
5. Affinity: Binding ability of the enzyme to the substrate (can be graphed as partial pressure
increases of the substrate against the affinity increases (0 to 1.0); affinity of binding of protein
and ligand is chemical attractive force between the protein and ligand.

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References:
1. Lehninger Principles of Biochemistry, 3rd Edition: David L. Nelson and Michael M. Cox
2. Biochemistry, 3rd edition: Garrett, Grisham
3. Daniel E (1995). "The Key–Lock Theory and the Induced Fit Theory". Angewandte Chemie
International Edition. 33 (2324): 2375–2378.
4. Sullivan SM (2008). "Enzymes with lid-gated active sites must operate by an induced fit
mechanism instead of conformational selection". Proceedings of the National Academy of
Sciences of the United States of America
5. Copeland, Robert A. (2013). "Drug–Target Residence Time". Evaluation of Enzyme Inhibitors in
Drug Discovery. John Wiley & Sons, Ltd. pp. 287–344. 

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