Cofactor (biochemistry)

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The succinate dehydrogenase complex showing several cofactors, including flavin, iron-sulfur centers, and heme. Succinate Dehydrogenase 1YQ3 Electron Carriers Labeled.png
The succinate dehydrogenase complex showing several cofactors, including flavin, iron–sulfur centers, and heme.

A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that assist in biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics. Cofactors typically differ from ligands in that they often derive their function by remaining bound.


Cofactors can be classified into two types: inorganic ions and complex organic molecules called coenzymes. [1] Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Some scientists limit the use of the term "cofactor" for inorganic substances; both types are included here. [2] [3] )

Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists of a coenzyme that is tightly (or even covalently) and permanently bound to a protein. [4] The second type of coenzymes are called "cosubstrates", and are transiently bound to the protein. Cosubstrates may be released from a protein at some point, and then rebind later. Both prosthetic groups and cosubstrates have the same function, which is to facilitate the reaction of enzymes and proteins. An inactive enzyme without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is called a holoenzyme. [5] [ page needed ] (The International Union of Pure and Applied Chemistry (IUPAC) defines "coenzyme" a little differently, namely as a low-molecular-weight, non-protein organic compound that is loosely attached, participating in enzymatic reactions as a dissociable carrier of chemical groups or electrons; a prosthetic group is defined as a tightly bound, nonpolypeptide unit in a protein that is regenerated in each enzymatic turnover. [6] )

Some enzymes or enzyme complexes require several cofactors. For example, the multienzyme complex pyruvate dehydrogenase [7] at the junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), cosubstrates nicotinamide adenine dinucleotide (NAD+) and coenzyme A (CoA), and a metal ion (Mg2+). [8]

Organic cofactors are often vitamins or made from vitamins. Many contain the nucleotide adenosine monophosphate (AMP) as part of their structures, such as ATP, coenzyme A, FAD, and NAD+. This common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world. It has been suggested that the AMP part of the molecule can be considered to be a kind of "handle" by which the enzyme can "grasp" the coenzyme to switch it between different catalytic centers. [9]


Cofactors can be divided into two major groups: organiccofactors, such as flavin or heme; and inorganic cofactors, such as the metal ions Mg2+, Cu+, Mn2+ and iron–sulfur clusters.

Organic cofactors are sometimes further divided into coenzymes and prosthetic groups . The term coenzyme refers specifically to enzymes and, as such, to the functional properties of a protein. On the other hand, "prosthetic group" emphasizes the nature of the binding of a cofactor to a protein (tight or covalent) and, thus, refers to a structural property. Different sources give slightly different definitions of coenzymes, cofactors, and prosthetic groups. Some consider tightly bound organic molecules as prosthetic groups and not as coenzymes, while others define all non-protein organic molecules needed for enzyme activity as coenzymes, and classify those that are tightly bound as coenzyme prosthetic groups. These terms are often used loosely.

A 1980 letter in Trends in Biochemistry Sciences noted the confusion in the literature and the essentially arbitrary distinction made between prosthetic groups and coenzymes group and proposed the following scheme. Here, cofactors were defined as an additional substance apart from protein and substrate that is required for enzyme activity and a prosthetic group as a substance that undergoes its whole catalytic cycle attached to a single enzyme molecule. However, the author could not arrive at a single all-encompassing definition of a "coenzyme" and proposed that this term be dropped from use in the literature. [10]

Inorganic cofactors

Metal ions

Metal ions are common cofactors. [11] The study of these cofactors falls under the area of bioinorganic chemistry. In nutrition, the list of essential trace elements reflects their role as cofactors. In humans this list commonly includes iron, magnesium, manganese, cobalt, copper, zinc, and molybdenum. [12] Although chromium deficiency causes impaired glucose tolerance, no human enzyme that uses this metal as a cofactor has been identified. [13] [14] Iodine is also an essential trace element, but this element is used as part of the structure of thyroid hormones rather than as an enzyme cofactor. [15] Calcium is another special case, in that it is required as a component of the human diet, and it is needed for the full activity of many enzymes, such as nitric oxide synthase, protein phosphatases, and adenylate kinase, but calcium activates these enzymes in allosteric regulation, often binding to these enzymes in a complex with calmodulin. [16] Calcium is, therefore, a cell signaling molecule, and not usually considered a cofactor of the enzymes it regulates. [17]

Other organisms require additional metals as enzyme cofactors, such as vanadium in the nitrogenase of the nitrogen-fixing bacteria of the genus Azotobacter , [18] tungsten in the aldehyde ferredoxin oxidoreductase of the thermophilic archaean Pyrococcus furiosus , [19] and even cadmium in the carbonic anhydrase from the marine diatom Thalassiosira weissflogii . [20] [21]

In many cases, the cofactor includes both an inorganic and organic component. One diverse set of examples is the heme proteins, which consist of a porphyrin ring coordinated to iron. [22]

IonExamples of enzymes containing this ion
Cupric Cytochrome oxidase
Ferrous or Ferric Catalase
Cytochrome (via Heme)
Magnesium Glucose 6-phosphatase
DNA polymerase
Manganese Arginase
Molybdenum Nitrate reductase
Xanthine oxidase
Nickel Urease
Zinc Alcohol dehydrogenase
Carbonic anhydrase
DNA polymerase
A simple [Fe2S2] cluster containing two iron atoms and two sulfur atoms, coordinated by four protein cysteine residues. 2Fe2S.png
A simple [Fe2S2] cluster containing two iron atoms and two sulfur atoms, coordinated by four protein cysteine residues.

Iron–sulfur clusters

Iron–sulfur clusters are complexes of iron and sulfur atoms held within proteins by cysteinyl residues. They play both structural and functional roles, including electron transfer, redox sensing, and as structural modules. [23]


Organic cofactors are small organic molecules (typically a molecular mass less than 1000 Da) that can be either loosely or tightly bound to the enzyme and directly participate in the reaction. [5] [24] [25] [26] In the latter case, when it is difficult to remove without denaturing the enzyme, it can be called a prosthetic group. It is important to emphasize that there is no sharp division between loosely and tightly bound cofactors. [5] Indeed, many such as NAD+ can be tightly bound in some enzymes, while it is loosely bound in others. [5] Another example is thiamine pyrophosphate (TPP), which is tightly bound in transketolase or pyruvate decarboxylase, while it is less tightly bound in pyruvate dehydrogenase. [27] Other coenzymes, flavin adenine dinucleotide (FAD), biotin, and lipoamide, for instance, are tightly bound. [28] Tightly bound cofactors are, in general, regenerated during the same reaction cycle, while loosely bound cofactors can be regenerated in a subsequent reaction catalyzed by a different enzyme. In the latter case, the cofactor can also be considered a substrate or cosubstrate.

Vitamins can serve as precursors to many organic cofactors (e.g., vitamins B1, B2, B6, B12, niacin, folic acid) or as coenzymes themselves (e.g., vitamin C). However, vitamins do have other functions in the body. [29] Many organic cofactors also contain a nucleotide, such as the electron carriers NAD and FAD, and coenzyme A, which carries acyl groups. Most of these cofactors are found in a huge variety of species, and some are universal to all forms of life. An exception to this wide distribution is a group of unique cofactors that evolved in methanogens, which are restricted to this group of archaea. [30]

Vitamins and derivatives

CofactorVitaminAdditional componentChemical group(s) transferredDistribution
Thiamine pyrophosphate [31] Thiamine (B1) pyrophosphate 2-carbon groups, α cleavage Bacteria, archaea and eukaryotes
NAD+ and NADP+ [32] Niacin (B3)ADP Electrons Bacteria, archaea and eukaryotes
Pyridoxal phosphate [33] Pyridoxine (B6)NoneAmino and carboxyl groups Bacteria, archaea and eukaryotes
Methylcobalamin [34] Vitamin B12 Methyl group acyl groups Bacteria, archaea and eukaryotes
Cobalamine [5] Cobalamine (B12)None hydrogen, alkyl groups Bacteria, archaea and eukaryotes
Biotin [35] Biotin (H)NoneCO2 Bacteria, archaea and eukaryotes
Coenzyme A [36] Pantothenic acid (B5)ADP Acetyl group and other acyl groups Bacteria, archaea and eukaryotes
Tetrahydrofolic acid [37] Folic acid (B9) Glutamate residues Methyl, formyl, methylene and formimino groups Bacteria, archaea and eukaryotes
Menaquinone [38] Vitamin KNone Carbonyl group and electrons Bacteria, archaea and eukaryotes
Ascorbic acid [39] Vitamin CNone Electrons Bacteria, archaea and eukaryotes
Flavin mononucleotide [40] Riboflavin (B2)None Electrons Bacteria, archaea and eukaryotes
Flavin adenine dinucleotide [40] Riboflavin (B2)ADP Electrons Bacteria, archaea and eukaryotes
Coenzyme F420 [41] Riboflavin (B2)Amino acids Electrons Methanogens and some bacteria


CofactorChemical group(s) transferredDistribution
Adenosine triphosphate [42] Phosphate group Bacteria, archaea and eukaryotes
S-Adenosyl methionine [43] Methyl group Bacteria, archaea and eukaryotes
Coenzyme B [44] Electrons Methanogens
Coenzyme M [45] [46] Methyl group Methanogens
Coenzyme Q [47] Electrons Bacteria, archaea and eukaryotes
Cytidine triphosphate [48] Diacylglycerols and lipid head groups Bacteria, archaea and eukaryotes
Glutathione [49] [50] Electrons Some bacteria and most eukaryotes
Heme [51] Electrons Bacteria, archaea and eukaryotes
Lipoamide [5] Electrons, acyl groups Bacteria, archaea and eukaryotes
Methanofuran [52] Formyl group Methanogens
Molybdopterin [53] [54] Oxygen atoms Bacteria, archaea and eukaryotes
Nucleotide sugars [55] Monosaccharides Bacteria, archaea and eukaryotes
3'-Phosphoadenosine-5'-phosphosulfate [56] Sulfate group Bacteria, archaea and eukaryotes
Pyrroloquinoline quinone [57] Electrons Bacteria
Tetrahydrobiopterin [58] Oxygen atom and electrons Bacteria, archaea and eukaryotes
Tetrahydromethanopterin [59] Methyl group Methanogens

Cofactors as metabolic intermediates

The redox reactions of nicotinamide adenine dinucleotide. NAD oxidation reduction.svg
The redox reactions of nicotinamide adenine dinucleotide.

Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups. [60] This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. [61] These group-transfer intermediates are the loosely bound organic cofactors, often called coenzymes.

Each class of group-transfer reaction is carried out by a particular cofactor, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. An example of this are the dehydrogenases that use nicotinamide adenine dinucleotide (NAD+) as a cofactor. Here, hundreds of separate types of enzymes remove electrons from their substrates and reduce NAD+ to NADH. This reduced cofactor is then a substrate for any of the reductases in the cell that require electrons to reduce their substrates. [32]

Therefore, these cofactors are continuously recycled as part of metabolism. As an example, the total quantity of ATP in the human body is about 0.1  mole. This ATP is constantly being broken down into ADP, and then converted back into ATP. Thus, at any given time, the total amount of ATP + ADP remains fairly constant. The energy used by human cells requires the hydrolysis of 100 to 150 moles of ATP daily, which is around 50 to 75 kg. In typical situations, humans use up their body weight of ATP over the course of the day. [62] This means that each ATP molecule is recycled 1000 to 1500 times daily.


Organic cofactors, such as ATP and NADH, are present in all known forms of life and form a core part of metabolism. Such universal conservation indicates that these molecules evolved very early in the development of living things. [63] At least some of the current set of cofactors may, therefore, have been present in the last universal ancestor, which lived about 4 billion years ago. [64] [65]

Organic cofactors may have been present even earlier in the history of life on Earth. [66] The nucleotide adenosine is present in cofactors that catalyse many basic metabolic reactions such as methyl, acyl, and phosphoryl group transfer, as well as redox reactions. This ubiquitous chemical scaffold has, therefore, been proposed to be a remnant of the RNA world, with early ribozymes evolving to bind a restricted set of nucleotides and related compounds. [67] [68] Adenosine-based cofactors are thought to have acted as interchangeable adaptors that allowed enzymes and ribozymes to bind new cofactors through small modifications in existing adenosine-binding domains, which had originally evolved to bind a different cofactor. [9] This process of adapting a pre-evolved structure for a novel use is known as exaptation .

A computational method, IPRO, recently predicted mutations that experimentally switched the cofactor specificity of Candida boidinii xylose reductase from NADPH to NADH. [69]


The first organic cofactor to be discovered was NAD+, which was identified by Arthur Harden and William Young 1906. [70] They noticed that adding boiled and filtered yeast extract greatly accelerated alcoholic fermentation in unboiled yeast extracts. They called the unidentified factor responsible for this effect a coferment. Through a long and difficult purification from yeast extracts, this heat-stable factor was identified as a nucleotide sugar phosphate by Hans von Euler-Chelpin. [71] Other cofactors were identified throughout the early 20th century, with ATP being isolated in 1929 by Karl Lohmann, [72] and coenzyme A being discovered in 1945 by Fritz Albert Lipmann. [73]

The functions of these molecules were at first mysterious, but, in 1936, Otto Heinrich Warburg identified the function of NAD+ in hydride transfer. [74] This discovery was followed in the early 1940s by the work of Herman Kalckar, who established the link between the oxidation of sugars and the generation of ATP. [75] This confirmed the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941. [76] Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that NAD+ linked metabolic pathways such as the citric acid cycle and the synthesis of ATP. [77]

Protein-derived cofactors

In a number of enzymes, the moiety that acts as a cofactor is formed by post-translational modification of a part of the protein sequence. This often replaces the need for an external binding factor, such as a metal ion, for protein function. Potential modifications could be oxidation of aromatic residues, binding between residues, cleavage or ring-forming. [78] These alterations are distinct from other post-translation protein modifications, such as phosphorylation, methylation, or glycosylation in that the amino acids typically acquire new functions. This increases the functionality of the protein; unmodified amino acids are typically limited to acid-base reactions, and the alteration of resides can give the protein electrophilic sites or the ability to stabilize free radicals. [78] Examples of cofactor production include tryptophan tryptophylquinone (TTQ), derived from two tryptophan side chains, [79] and 4-methylidene-imidazole-5-one (MIO), derived from an Ala-Ser-Gly motif. [80] Characterization of protein-derived cofactors is conducted using X-ray crystallography and mass spectroscopy; structural data is necessary because sequencing does not readily identify the altered sites.

Non-enzymatic cofactors

The term is used in other areas of biology to refer more broadly to non-protein (or even protein) molecules that either activate, inhibit, or are required for the protein to function. For example, ligands such as hormones that bind to and activate receptor proteins are termed cofactors or coactivators, whereas molecules that inhibit receptor proteins are termed corepressors. One such example is the G protein-coupled receptor family of receptors, which are frequently found in sensory neurons. Ligand binding to the receptors activates the G protein, which then activates an enzyme to activate the effector. [81] In order to avoid confusion, it has been suggested that such proteins that have ligand-binding mediated activation or repression be referred to as coregulators. [82]

See also

Related Research Articles

<span class="mw-page-title-main">Enzyme</span> Large biological molecule that acts as a catalyst

Enzymes are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called enzymology and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties.

<span class="mw-page-title-main">Glycolysis</span> Catabolic pathway

Glycolysis is the metabolic pathway that converts glucose into pyruvate, and in most organisms, occurs in the liquid part of cells, the cytosol. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

<span class="mw-page-title-main">Metabolism</span> Set of chemical reactions in organisms

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism.

<span class="mw-page-title-main">Nucleotide</span> Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

<span class="mw-page-title-main">Oxidative phosphorylation</span> Metabolic pathway

Oxidative phosphorylation or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis.

<span class="mw-page-title-main">Coenzyme A</span> Coenzyme, notable for its synthesis and oxidation role

Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).

<span class="mw-page-title-main">Flavin group</span> Group of chemical compounds

Flavins refers generally to the class of organic compounds containing the tricyclic heterocycle isoalloxazine or its isomer alloxazine, and derivatives thereof. The biochemical source of flavin is the vitamin riboflavin. The flavin moiety is often attached with an adenosine diphosphate to form flavin adenine dinucleotide (FAD), and, in other circumstances, is found as flavin mononucleotide, a phosphorylated form of riboflavin. It is in one or the other of these forms that flavin is present as a prosthetic group in flavoproteins.

<span class="mw-page-title-main">Active site</span> Active region of an enzyme

In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the binding site, and residues that catalyse a reaction of that substrate, the catalytic site. Although the active site occupies only ~10–20% of the volume of an enzyme, it is the most important part as it directly catalyzes the chemical reaction. It usually consists of three to four amino acids, while other amino acids within the protein are required to maintain the tertiary structure of the enzymes.

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide</span> Chemical compound which is reduced and oxidized

Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD+ and NADH (H for hydrogen), respectively.

<span class="mw-page-title-main">Biomolecule</span> Molecule that is produced by a living organism

A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include the primary metabolites which are large macromolecules such as proteins, carbohydrates, lipids, and nucleic acids, as well as small molecules such as vitamins and hormones. A more general name for this class of material is biological materials. Biomolecules are an important element of living organisms, those biomolecules are often endogenous, produced within the organism but organisms usually need exogenous biomolecules, for example certain nutrients, to survive.

A prosthetic group is the non-amino acid component that is part of the structure of the heteroproteins or conjugated proteins, being tightly linked to the apoprotein.

<span class="mw-page-title-main">Pyruvate dehydrogenase complex</span> Three-enzyme complex responsible for pyruvate decarboxylation

Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the citric acid cycle. Pyruvate decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it also involves the oxidation of pyruvate.

<span class="mw-page-title-main">Pyrroloquinoline quinone</span> Chemical compound

Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor and antioxidant.

<span class="mw-page-title-main">Pyridoxal phosphate</span> Active form of vitamin B6

Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.

<span class="mw-page-title-main">Rossmann fold</span>

The Rossmann fold is a tertiary fold found in proteins that bind nucleotides, such as enzyme cofactors FAD, NAD+, and NADP+. This fold is composed of alternating beta strands and alpha helical segments where the beta strands are hydrogen bonded to each other forming an extended beta sheet and the alpha helices surround both faces of the sheet to produce a three-layered sandwich. The classical Rossmann fold contains six beta strands whereas Rossmann-like folds, sometimes referred to as Rossmannoid folds, contain only five strands. The initial beta-alpha-beta (bab) fold is the most conserved segment of the Rossmann fold. The motif is named after Michael Rossmann who first noticed this structural motif in the enzyme lactate dehydrogenase in 1970 and who later observed that this was a frequently occurring motif in nucleotide binding proteins.

<span class="mw-page-title-main">Flavin adenine dinucleotide</span> Redox-active coenzyme

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex.

<span class="mw-page-title-main">Flavoprotein</span> Protein family

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. The flavoproteins are some of the most-studied families of enzymes.

A holoprotein or conjugated protein is an apoprotein combined with its prosthetic group.

<span class="mw-page-title-main">Enzyme catalysis</span> Catalysis of chemical reactions by specialized proteins known as enzymes

Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, called the active site.

<span class="mw-page-title-main">Vitamin B12-binding domain</span> Type of protein domain

In molecular biology, the vitamin B12-binding domain is a protein domain which binds to cobalamin. It can bind two different forms of the cobalamin cofactor, with cobalt bonded either to a methyl group (methylcobalamin) or to 5'-deoxyadenosine (adenosylcobalamin). Cobalamin-binding domains are mainly found in two families of enzymes present in animals and prokaryotes, which perform distinct kinds of reactions at the cobalt-carbon bond. Enzymes that require methylcobalamin carry out methyl transfer reactions. Enzymes that require adenosylcobalamin catalyse reactions in which the first step is the cleavage of adenosylcobalamin to form cob(II)alamin and the 5'-deoxyadenosyl radical, and thus act as radical generators. In both types of enzymes the B12-binding domain uses a histidine to bind the cobalt atom of cobalamin cofactors. This histidine is embedded in a DXHXXG sequence, the most conserved primary sequence motif of the domain. Proteins containing the cobalamin-binding domain include:


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