Editing Active site (section)

==Mechanisms involved in Catalytic process==

===Approximation of the reactant===

During enzyme catalytic reaction, the substrate and active site are brought together in a close proximity. This approach has various purposes. Firstly, when substrates bind within the active site the [[Thermodynamic activity|effective concentration]] of it significantly increases than in solution. This means the number of substrate molecules involved in the reaction is also increased. This process also reduces the [[solvation|desolvation energy]] required for the reaction to occur. In solution substrate molecules are surrounded by solvent molecules and energy is required for enzyme molecules to replace them and contact with the substrate. Since bulk molecules can be excluded from the active site this energy output can be minimised. Next, the active site is designed to reorient the substrate to reduce the activation energy for the reaction to occur. The alignment of the substrate, after binding, is locked in a high energy state and can proceed to the next step. In addition, this binding is favoured by [[entropy]] as the energy cost associated with solution reaction is largely eliminated since solvent cannot enter active site. In the end, the active site may manipulate the [[Molecular orbital]] of the substrate into a suitable orientation to reduce activation energy.<ref name=":1" />{{Rp|155–8}}

The electrostatic states of substrate and active site must be complementary to each other. A polarized negatively charged amino acid side chain will repel uncharged substrate. But if the transition state involves the formation of an [[cation|ion]] centre then the side chain will now produce a favourable interaction.

===Covalent catalysis===

Many enzymes including [[serine protease]], [[cysteine protease]], [[protein kinase]] and [[phosphatase]] evolved to form transient covalent bonds between them and their substrates to lower the activation energy and allow the reaction to occur. This process can be divided into 2 steps: formation and breakdown. The former step is rate-limit step while the later step is needed to regenerate intact enzyme.<ref name=":1" />{{Rp|158}}

'''Nucleophilic catalysis''': This process involves the donation of electrons from the enzyme's [[nucleophile]] to a substrate to form a covalent bond between them during the transition state. The strength of this interaction depends on two aspects.: the ability of the nucleophilic group to donate electrons and the [[electrophile]] to accept them. The former one is mainly affected by the basicity(the ability to donate electron pairs) of the species while the later one is in regard to its [[acid dissociation constant|p''K''<sub>a</sub>]]. Both groups are also affected by their chemical properties such as [[polarizability]], [[electronegativity]] and [[ionization energy|ionization potential]]. Amino acids that can form nucleophile including [[serine]], [[cysteine]], [[aspartate]] and [[glutamine]].{{citation needed|date=June 2024}}

'''Electrophilic catalysis''': The mechanism behind this process is exactly same as nucleophilic catalysis except that now amino acids in active site act as [[electrophile]] while substrates are [[nucleophiles]]. This reaction usually requires cofactors as the amino acid side chains are not strong enough in attracting electrons.

===Metal ions===
[[Metal ions in aqueous solution|Metal ions]] have multiple roles during the reaction. Firstly it can bind to negatively charged substrate groups so they will not repel electron pairs from active site's nucleophilic groups. It can attract negatively charged electrons to increase [[electrophilicity]]. It can also bridge between active site and substrate. At last, they may change the conformational structure of the substrate to favour reaction.
<ref name=":1" />{{Rp|158}}

===Acid/base catalysis===
In some reactions, [[protons]] and [[hydroxide]] may directly act as acid and base in term of specific acid and specific base catalysis. But more often groups in substrate and active site act as Brønsted–Lowry acid and base. This is called general acid and general base theory. The easiest way to distinguish between them is to check whether the [[reaction rate]] is determined by the concentrations of the general acid and base. If the answer is yes then the reaction is the general type. Since most enzymes have an optimum [[pH]] of 6 to 7, the amino acids in the side chain usually have a [[Acid dissociation constant|p''K''<sub>a</sub>]] of 4~10. Candidate include [[aspartate]], [[glutamate]], [[histidine]], [[cysteine]]. These acids and bases can stabilise the nucleophile or electrophile formed during the catalysis by providing positive and negative charges.<ref name=":1" />{{Rp|164–70}}

===Conformational distortion===
Quantitative studies of enzymatic reactions often found that the acceleration of chemical reaction speed cannot be fully explained by existing theories like the approximation, acid/base catalysis and electrophile/nucleophile catalysis. And there is an obvious paradox: in reversible enzymatic reaction if the active site perfectly fits the substrates then the [[Chemical equilibrium|backward reaction]] will be slowed since products cannot fit perfectly into the active site. So conformational distortion was introduced and argues that both active site and substrate can undergo conformational changes to fit with each other all the time.<ref name=":1" />{{Rp|170–5}}

===Preorganised active site complementarity to the transition state===
This theory is a little similar to the Lock and Key Theory, but at this time the active site is preprogrammed to bind perfectly to substrate in transition state rather than in ground state. The formation of transition state within the solution requires a large amount of energy to relocate solvent molecules and the reaction is slowed. So the active site can substitute solvent molecules and surround the substrates to minimize the counterproductive effect imposed by the solution. The presence of charged groups with the active site will attract substrates and ensure electrostatic complementarity.<ref name=":1" />{{Rp|176–8}}