Substrate analog
Encyclopedia
Transition state analogs (transition state analogues), are chemical compound
s with a chemical structure
that resembles the transition state
of a substrate molecule in an enzyme-catalyzed
chemical reaction
. Transition state analogs usually do not undergo a chemical reaction and can act as enzyme inhibitor
s by blocking their active site
. Examples of drug
s that are transition state analog inhibitors include flu medications such as the neuraminidase inhibitor
oseltamivir
and the HIV protease inhibitors saquinavir
in the treatment of AIDS.
by stabilizing a high energy transition state
intermediate which lowers the activation energy
of the reaction. Transition state analogs that mimick this high-affinity intermediate but that do not undergo the catalyzed chemical reaction can therefore bind much stronger to an enzyme than simple substrate or product analogs.
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
s with a chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
that resembles the transition state
Transition state
The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules will always...
of a substrate molecule in an enzyme-catalyzed
Enzyme catalysis
Enzyme catalysis is the catalysis of chemical reactions by specialized proteins known as enzymes. Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions....
chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
. Transition state analogs usually do not undergo a chemical reaction and can act as enzyme inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
s by blocking their active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
. Examples of drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s that are transition state analog inhibitors include flu medications such as the neuraminidase inhibitor
Neuraminidase inhibitor
Neuraminidase inhibitors are a class of antiviral drugs targeted at the influenza virus, which work by blocking the function of the viral neuraminidase protein, thus preventing the virus from reproducing by budding from the host cell....
oseltamivir
Oseltamivir
Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...
and the HIV protease inhibitors saquinavir
Saquinavir
Saquinavir is an antiretroviral drug used in HIV therapy. It falls in the protease inhibitor class. Two formulations have been marketed:*a hard-gel capsule formulation of the mesylate, with trade name Invirase, which requires combination with ritonavir to increase the saquinavir bioavailability;*a...
in the treatment of AIDS.
Mechanism
Like all catalysts, enzymes work by increasing the chemical reaction rateReaction rate
The reaction rate or speed of reaction for a reactant or product in a particular reaction is intuitively defined as how fast or slow a reaction takes place...
by stabilizing a high energy transition state
Transition state
The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules will always...
intermediate which lowers the activation energy
Activation energy
In chemistry, activation energy is a term introduced in 1889 by the Swedish scientist Svante Arrhenius that is defined as the energy that must be overcome in order for a chemical reaction to occur. Activation energy may also be defined as the minimum energy required to start a chemical reaction...
of the reaction. Transition state analogs that mimick this high-affinity intermediate but that do not undergo the catalyzed chemical reaction can therefore bind much stronger to an enzyme than simple substrate or product analogs.
See also
- EnzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
- Structural analog, compounds with similar chemical structure
- Enzyme inhibitorEnzyme inhibitorAn enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
- Substrate analogSubstrate analogTransition state analogs , are chemical compounds with a chemical structure that resembles the transition state of a substrate molecule in an enzyme-catalyzed chemical reaction. Transition state analogs usually do not undergo a chemical reaction and can act as enzyme inhibitors by blocking their...
- Suicide inhibitor