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territory over which rule or control is exercised; "his domain extended into Europe"; "he made it the law of the land" (同)demesne, land
(mathematics) the set of values of the independent variable for which a function is defined (同)domain of a function
relating to or causing or involving catalysis; "catalytic reactions"

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(国の)領地,領土;(個人の)所有地 / (関心・活動などの)範囲,分野 / (個人・一族の)所有地 / (数学で)変域(関数の独立変数がとる値の集合)
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/16 14:17:33」(JST)

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Organisation of enzyme structure and lysozyme example. Binding sites in blue, catalytic site in red and peptidoglycan substrate in black. (PDB 9LYZ)

In biology, the active site is a small port in an enzyme where substrate molecules bind and undergo a chemical reaction. This chemical reaction occurs when a substrate collides with and slots into the active site of an enzyme. The active site is usually found in a 3-D groove or pocket of the enzyme, lined with amino acid residues (or nucleotides in RNA enzymes). These residues are involved in recognition of the substrate. Residues that directly participate in the catalytic reaction mechanism are called active site residues. After an active site has been involved in a reaction, it can be used again.^[1] Many (more than 68%) enzymes have deeply buried active sites, which can be accessed by a substrate via access channels.^[2]

Binding

Usually, an enzyme molecule has only one active site, and the active site fits with one specific type of substrate. Enzymes can be denatured by high temperatures or extreme pH values, meaning that the active site changes shape and does not fit its substrate molecules.^[3] A tighter fit between an active site and the substrate molecule is believed to increase efficiency of a reaction.^[4]

There are two proposed models of how enzymes fit to their specific substrate: the lock and key model and the induced fit model.

Lock and key hypothesis

Emil Fischer's lock and key model assumes that the active site is a perfect fit for a specific substrate and that once the substrate binds to the enzyme no further modification occurs.^[5]

Induced fit hypothesis

Daniel Koshland's theory of enzyme-substrate binding is that the active site and the binding portion of the substrate are not exactly complementary.^[5] The induced fit model is a development of the lock-and-key model and assumes that an active site is flexible and it changes shape until the substrate is completely bound. The substrate is thought to induce a change in the shape of the active site. The hypothesis also predicts that the presence of certain residues (amino acids) in the active site will encourage the enzyme to locate the correct substrate. Conformational changes may then occur as the substrate is bound. After the products of the reaction move away from the enzyme, the active site returns to its initial shape.

Chemistry

Substrates bind to the active site of the enzyme through hydrogen bonds, hydrophobic interactions, temporary covalent interactions (van der Waals) or a combination of all of these to form the enzyme-substrate complex. Residues of the active site will act as donors or acceptors of protons or other groups on the substrate to facilitate the reaction. In other words, the active site modifies the reaction mechanism in order to change the activation energy of the reaction. An enzyme binding to a substrate will lower the energy barrier that normally stops the reaction from happening. The product is usually unstable in the active site due to steric hindrances that force it to be released and return the enzyme to its initial unbound state.

Cofactors

Enzymes can use cofactors as ‘helper molecules’. Coenzymes are one example of cofactors. Coenzymes bind to the enzyme temporarily and are released after the reaction has occurred. Metal ions are another type of cofactor.

Inhibitors

Inhibitors disrupt the interaction between enzyme and substrate, slowing down the rate of a reaction. There are different types of inhibitor, including both reversible and irreversible forms. Reversible inhibitors can be competitive or non-competitive. Competitive reversible inhibitors have a similar shape to the substrate and bind to the enzyme’s active site temporarily, blocking entry of the actual substrate into the active site. Non-competitive reversible inhibitors bind to the enzyme however not in the active site. Despite not interacting with the active site, non-competitive inhibitors do reduce the rate of the reaction because they cause the enzyme to change shape. Irreversible inhibitors bind permanently to the enzyme, blocking access to active sites and therefore reducing the rate of the reaction.

	Example	Binds active site?	Reduces rate of reaction?
Competitive reversible inhibitor	HIV protease inhibitors	Yes	Yes
Non-competitive reversible inhibitor	Heavy metals such as lead and mercury	No	Yes
Irreversible inhibitor	Cyanide	Yes	Yes

Active sites in drug discovery

Identification of active sites is crucial in the process of drug discovery. The 3-D structure of the enzyme is analysed to identify active sites and design drugs which can fit into them. Proteolytic enzymes are targets for some drugs, such as protease inhibitors, which include drugs against AIDS and hypertension.^[6] These protease inhibitors bind to an enzyme's active site and block interaction with natural substrates.^[7] An important factor in drug design is the strength of binding between the active site and an enzyme inhibitor.^[8]

Active sites can be mapped to aid design of new drugs such as enzyme inhibitors. This involves description of the size of an active site and the number and properties of sub-sites, such as details of the binding interaction.^[6] Modern database technology called CPASS (Comparison of Protein Active Site Structures) however allows us to compare active sites in more detail and to look at structural similarity using software.^[9]

Allosteric sites

An allosteric site is a site on an enzyme, unrelated to its active site, which can bind an effector molecule. This interaction is another mechanism of enzyme regulation. Allosteric modification usually happens in proteins with more than one subunit. Allosteric interactions are often present in metabolic pathways and are beneficial in that they allow one step of a reaction to regulate another step.^[7] They allow an enzyme to have a range of molecular interactions, other than the highly specific active site.^[7]

References

^ Alberts, B (2010). Essential Cell Biology. Garland Science. p. 91.
^ Pravda L., Berka K., Svobodova Varekova R, Banas P., Laskowski R.A., Koca J., Otyepka M. (2014). "Anatomy of Enzyme Channels". BMC Bioinformatics 15: 379. doi:10.1186/s12859-014-0379-x.
^ Campbell, P (2006). Biochemistry Illustrated. Elsevier. pp. 83–85.
^ Kool ET (1984). "Active site tightness and substrate fit in DNA replication". Annual Review of Biochemistry 71: 191–219. doi:10.1146/annurev.biochem.71.110601.135453.
^ ^a ^b 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 105: 13829–13834. doi:10.1073/pnas.0805364105.
^ ^a ^b Schechter I (2005). "Mapping of the active site of proteases in the 1960s and rational design of inhibitors/drugs in the 1990s". Current Protein and Peptide Science 6: 501–512. doi:10.2174/138920305774933286.
^ ^a ^b ^c DeDecker BS (2000). "Allosteric drugs: thinking outside the active-site box". Chemistry and Biology 7: 103–107. doi:10.1016/S1074-5521(00)00115-0.
^ Zuercher M (2008). "Structure-Based Drug Design: Exploring the Proper Filling of Apolar Pockets at Enzyme Active Sites". Journal of Organic Chemistry 73: 4345–4361. doi:10.1021/jo800527n.
^ Powers R (2006). "Comparison of protein active site structures for functional annotation of proteins and drug design". Proteins : Structure, Function, and Bioinformatics 65: 124–135. doi:10.1002/prot.21092.

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リンク元	「触媒領域」「catalytic subunit」「触媒ドメイン」「catalytic core」「catalytic region」
関連記事	「domain」「catalytic」「domains」