Catalytic enzyme is an increase in the rate of chemical reactions by the protein's active site. The protein catalyst (enzyme) can be part of a multi-subunit complex, and/or can be attributed temporarily or permanently with Cofactor (eg adenosine triphosphate). The catalysis of biochemical reactions in cells is very important because of the very low reaction rates of unaccumulated reactions at room temperature and pressure. The main driver of protein evolution is the optimization of catalytic activity such as through the dynamics of proteins.
The mechanism of enzyme catalysis is in principle similar to other types of chemical catalysis. By providing an alternative reaction route, the enzyme reduces the energy required to achieve the highest energy transition state of the reaction. The reduction of activation energy (Ea) increases the number of reactant molecules that reach sufficient energy levels, so they reach the activation energy and form the product. As with any other catalyst, the enzyme is not consumed during the reaction (as a substrate) but is recycled in such a way that one enzyme performs many catalysis rounds.
Video Enzyme catalysis
Induced fit
The preferred model for substrate-enzyme interactions is the induced fit model. This model proposes that early interactions between enzymes and substrates are relatively weak, but these weak interactions quickly induce conformational changes in enzymes that strengthen binding.
The advantages of induced fit mechanisms arise because of the stabilizing effects of strong enzyme bonds. There are two different substrate binding mechanisms: uniform binding, which has strong substrate binding, and differential binding, which has a strong transition bonding state. The stable effect of uniform binding increases substrate bonding and binding transition states, while differential binding only increases the affinity of binding of the transition state. Both are used by enzymes and have been evolved to minimize the activation energy of the reaction. The saturated enzyme, that is, has a high affinity substrate binding, requiring differential binding to reduce the activation energy, whereas the unbound enzyme of the small substrate may use differential or uniform binding.
This effect has caused most proteins to use a differential binding mechanism to reduce the activation energy, so most of the substrate has a high affinity for the enzyme while in transition state. The differential binding is performed by the induced fit mechanism - the first substrate is weakly bound, then the enzyme alters the conformation increasing the affinity to the transition state and stabilizes, thereby reducing the activation energy to achieve it.
It is important to explain, however, that the concept of induced fit can not be used to rationalize catalysis. That is, chemical catalysis is defined as a reduction of Ea ? (when the system is already in ES ? ) relative to Ea ? in a reaction that does not accumulate in water (without enzymes). The induced fits only show that the barrier is lower in the closed form of the enzyme but it does not tell us what is the reason for the reduction of the barrier.
Induced fit may be beneficial for the loyalty of molecular recognition in the face of competition and noise through conformational proofreading mechanisms.
Maps Enzyme catalysis
Mechanism of alternative reaction routes
This conformational change also carries catalytic residues at an active site close to the chemical bonds on the substrate that will be altered in the reaction. After binding occurs, one or more of the catalysis mechanisms decreases the energy of the transition state of the reaction, providing an alternative chemical pathway for the reaction. There are six possible "over the barrier" katalysis mechanisms as well as the "through the barrier" mechanism:
Distance and orientation
Interaction of the enzymes aligns the reactive chemical groups and holds them close together in optimal geometry, which increases the rate of reaction. This reduces the entropy of the reactants and thereby makes the addition or transfer reaction less favorable, due to the overall reduction of entropy when the two reactants become one product.
This effect is analogous to the effective increase of reagent concentration. The binding of the reagent to the enzyme provides an intramolecular reaction character, which provides a very large increase in rate.
However, the situation may be more complex, as modern computational studies have determined that traditional examples of proximity effects can not be attributed directly to the effects of entropic enzymes. Also, original entropy proposals have been found to exaggerate the contribution of entropy orientation to catalysis.
Proton donor or acceptor
The proton donors and acceptor, ie acids and bases, can donate and receive protons to stabilize the charge that develops in a transition state. This usually has the effect of activating the nucleophile and electrophile groups, or stabilizing the leaving group. Histidine is often a residue involved in this acid/base reaction, because it has a pKa that is close to neutral pH and therefore can receive and donate protons.
Many reaction mechanisms involve acid/base catalysis which assumes a substantially altered pKa. Changes to this pKa are made possible through the local environment of the residue.
pKa can also be significantly affected by the surrounding environment, as long as the fundamental residue in the solution can act as a proton donor, and vice versa.
It is important to clarify that the pKa modification is a purely part of the electrostatic mechanism. Furthermore, the catalytic effect of the above example is mainly related to the reduction of pKa from oxyion and the increase in histidine pKa, whereas the transfer of proton from serine to histidine is not significantly catalyzed, as it is not a rate-determining barrier.
Electrostatic catalysis
Stabilization of the charged transition state can also be by residuals on active sites forming ionic bonds (or partial ionic charge interactions) with intermediaries. This bond may be derived from acid or base side chains found in amino acids such as lysine, arginine, aspartic acid or glutamic acid or derived from metal cofactors such as zinc. Metal ions are very effective and can reduce the pKa of water enough to make it an effective nucleophile.
Computer systematic simulation studies establish that the electrostatic effect provides, by far, the greatest contribution to catalysis. In particular, it has been found that enzymes provide a more polar environment than water, and that the ion transition state is stabilized by fixed dipoles. This is very different from the stabilization of the transition state in water, where water molecules have to pay with "energy reorganization". To stabilize ion and charge status. Thus, catalysis is associated with the fact that the polar enzyme groups are prearranged
The magnitude of the electrostatic field provided by the enzyme's active site has been shown to be highly correlated with elevated catalytic levels of the enzyme.
Substrate binding usually excludes water from the active site, thereby lowering the local dielectric constant into an organic solvent. It strengthens the electrostatic interaction between the charged/polar substrate and the active site. In addition, research has shown that the charge distribution of active sites is arranged in such a way as to stabilize the transition state of the catalyzed reaction. In some enzymes, this charge distribution seems to serve to guide the polar substrate to its binding site so that the rate of this enzymatic reaction is greater than the visible control-diffusion limit.
covalent catalysis
Covalent catalysis involves the substrate forming a transient covalent bond with a residue on the enzyme's active site or with a cofactor. This adds an additional covalent addition to the reaction, and helps reduce energy from the next transition state of the reaction. The covalent bond must, at a later stage in the reaction, be damaged to regenerate the enzyme. This mechanism is used by enzyme catalytic trials such as proteases such as chymotrypsin and trypsin, in which acyl-enzyme intermediates are formed. An alternative mechanism is the formation of schiff using free amines from lysine residues, as seen in aldolase enzyme during glycolysis.
Some enzymes utilize non-amino acid cofactors such as pyridoxal phosphate (PLP) or thiamin pyrophosphate (TPP) to form covalent intermediates with reactant molecules. The function of such covalent intermediates to reduce the energy of the later transition state, similar to how the covalent intermediates formed with active amino acid residues allow stabilization, but the ability of the cofactor enables the enzyme to react only amino acid residues. Enzymes using such cofactors include aspartate-dependent aspartate transaminase enzymes that depend on PLP and pyruvate-dependent dehydrogenase enzymes.
Rather than lowering the activation energy for the reaction pathway, covalent catalysis provides an alternative pathway for reactions (through to covalent intermediates) and so different from true catalysis. For example, the energy from covalent bonds to serine molecules in chymotrypsin should be compared with well-understood covalent bonds to nucleophiles in the un-catalyzed reaction solution. The correct proposal of covalent catalysis (where a barrier is lower than an appropriate barrier in solution) will require, for example, partial covalent bonding to the transition state by enzyme groups (eg, very strong hydrogen bonds), and such an effect does not contribute significantly to catalysis.
Metal ion catalysis
Metal ions at active sites participate in catalysis by coordinating stabilization and shielding of charge. Because of the positive charge of the metal, only the negative charge can be stabilized through metal ions. However, metal ions are advantageous in biological catalysis because they are unaffected by changes in pH. Metal ions can also act to ionize water by acting as Lewis acid. Metal ions can also be oxidizing agents and reductions.
Strain bond
This is the main effect of induced fit binding, in which the affinity of the enzyme to the transition state is greater than that of the substrate itself. This induces a structural rearrangement that filters the substrate bond to a position closer to the conformation of the transition state, thereby lowering the energy difference between the substrate and the transition state and helping to catalyze the reaction.
However, this strain effect, in fact, the effect of the destabilization of the ground state, rather than the effect of stabilization of the transition state. Furthermore, enzymes are very flexible and they can not apply large strain effects.
In addition to the bonding strain on the substrate, the bond strain can also be induced in the enzyme itself to activate the residue on the active site.
Quantum tunneling
This traditional "over the barrier" mechanism has been challenged in some cases by modeling and observing "tunneling quantum" mechanisms. Some enzymes operate with kinetics that are faster than what is expected by the classics? G ? . In the "through barrier" model, protons or electrons can penetrate the activation barrier. Quantum tunneling for protons has been observed in tryptamine oxidation by aromatic amine dehydrogenase.
Interestingly, quantum tunneling does not appear to provide a major catalytic advantage, since the contribution of tunneling is similar in the catalyst reaction and does not accumulate in solution. However, the contribution of tunneling (typically increasing the rate constant by a factor of ~ 1000 compared to the reaction rate for the classical route 'above the barrier') is probably important for the survival of biological organisms. It emphasizes the importance of tunneling reactions in biology.
In 1971-1972, the first quantum mechanical model of enzyme catalysis was formulated.
Enzyme is on
The enzyme-substrate enzyme binding energy can not be considered as the external energy required for substrate activation. The high energy content enzyme may first transfer some of the specific energetic groups X 1 from the enzyme catalytic site to the last place of the first bonded reactant, then another group X 2 of the second bonded reactant ( or from a second group of single reactants) must be transferred to the active site to complete substrate conversion to the product and regeneration of the enzyme.
We can present the entire enzymatic reaction as a reaction of two couplings:
It can be seen from the reaction ( 1 ) that the group X 1 of the active enzyme appears in the product due to possible exchange reactions in the enzyme to avoid electrostatic inhibition and atomic repulsion. So we represent the active enzyme as a strong reactant of the enzymatic reaction. The reaction ( 2 ) indicates an incomplete substrate conversion because the group X 2 remains inside the enzyme. This approach as a previously proposed idea relies on highly hypothetical enzymatic conversion (perfect catalytic enzyme).
An important point for verifying the current approach is that the catalyst must be an enzyme complex with the reaction transfer group. This chemical aspect is supported by well-studied mechanisms of several enzymatic reactions. Let us consider the hydrolysis reaction of peptide bonds catalyzed by pure proteins? -chymgrypsin (an enzyme that works without cofactors), which is a member of the well-studied serine protease family, see.
We present experimental results for this reaction as two chemical steps:
where S 1 is polypeptide, P 1 and P 2 is the product. The first chemical step ( 3 ) includes the formation of covalent acyl enzymes. The second step ( 4 ) is the deacylation step. It is important to note that group H, initially found in enzymes, but not in water, appears in the product before the hydrolysis step, therefore it can be considered as an additional group of enzymatic reactions.
Thus, the reaction ( 3 ) indicates that the enzyme acts as a strong reactant of the reaction. According to the proposed concept, H transport of the enzyme encourages the conversion of the first reactant, the first initial chemical bond breakdown (between groups P 1 and P 2 ). The hydrolysis step leads to both chemical bond damage and enzyme regeneration.
The proposed chemical mechanism does not depend on the concentration of substrate or product in the medium. However, their concentration shifts primarily result in free energy changes in the first and last step of the reaction ( 1 ) and ( 2 ) due to changes in the free energy content of each molecule, whether S or P, in aqueous solution. This approach corresponds to the following muscle contraction mechanism. The final step of hydrolysis of ATP in the skeletal muscle is the release of the product caused by the myosin head association with actin. Closure of the actin-binding blockage during an association reaction is structurally coupled with the opening of a nucleotide-binding sac on the myosin active site.
In particular, the last steps of ATP hydrolysis include rapid release of phosphate and slow release of ADP. The release of phosphate anions of ADP anions bound into aqueous solutions can be considered as an exergonic reaction because the phosphate anion has a low molecular mass.
Thus, we come to the conclusion that the major release of the inorganic phosphate H 2 PO 4 - leads to the transformation of an important part of the free energy of the hydrolysis of ATP into the kinetic energy of the dissolved phosphate, producing an active stream. This local mechano-chemical transduction assumption matches the mechanism of muscle contraction of the Tirosh, in which muscle strength comes from the integrated action of the active stream made by ATP hydrolysis.
Examples of catalytic mechanisms
In fact, most enzyme mechanisms involve combinations of several types of catalysis.
Triose phosphate isomerase
Triose phosphate isomerase (EC 5.3.1.1) catalyzes the reversible interconversion of the two phosphate triose isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.
Trypsin
Trypsin (EC 3.4.21.4) is a serine protease that cuts the protein substrate after lysine or arginine residues using catalytic triads to perform covalent catalysis, and the oxyanion hole to stabilize the accumulation of charge in the transition state.
Aldolase
Aldolase (EC 4.1.2.13) catalyzes the breakdown of fructose 1,6-bisphosphate (F-1,6-BP) into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP).
Enzyme Disorder
The emergence of a single molecule study led in 2010 to the observation that unregulated enzyme movements increase with increasing substrate concentrations and an increase in the enthalpy of reactions. Subsequent observations indicate that this increase in diffusivity is driven by temporary displacement of enzyme mass centers, resulting in "reverse effects that induce enzymes".
Reaction similarities
The similarity between enzymatic (EC) reactions can be calculated by using a change of bond, reaction center or substructure metric (EC-BLAST).
See also
- Triad Catalytic
- Enzyme assay
- Enzyme Kinetics
- Promiscuity enzyme
- Dynamics of protein
- Pseudoenzymes, which are ubiquity even though they are not catalytically active show omic implications
- Quantum tunneling
- Proteolysis Map
- Completed crystallographic time
References
Further reading
- Alan Fersht, Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Preparation. W. H. Freeman, 1998. ISBNÃ, 0-7167-3268-8
- Special Issues Transactions of Philosophy B on Quantum catalysis in freely available enzymes.
Source of the article : Wikipedia
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