Molybdopterins are a class of cofactors found in most

molybdenum Molybdenum is a chemical element; it has Symbol (chemistry), symbol Mo (from Neo-Latin ''molybdaenum'') and atomic number 42. The name derived from Ancient Greek ', meaning lead, since its ores were confused with lead ores. Molybdenum minerals hav ...

-containing and all

tungsten Tungsten (also called wolfram) is a chemical element; it has symbol W and atomic number 74. It is a metal found naturally on Earth almost exclusively in compounds with other elements. It was identified as a distinct element in 1781 and first ...

-containing enzymes. Synonyms for molybdopterin are: MPT and pyranopterin-dithiolate. The nomenclature for this biomolecule can be confusing: Molybdopterin itself contains no molybdenum; rather, this is the name of the ligand (a ''

pterin Pterin is a heterocyclic compound composed of a pteridine ring system, with a " keto group" (a lactam) and an amino group on positions 4 and 2 respectively. It is structurally related to the parent bicyclic heterocycle called pteridine. Pter ...

'') that will bind the active metal. After molybdopterin is eventually complexed with molybdenum, the complete ligand is usually called

molybdenum cofactor A molybdenum cofactor is a biochemical Cofactor (biochemistry), cofactor that contains molybdenum. Examples include: * Molybdopterin (or, strictly speaking, the molybdopterin-molybdenum-complex), the organophosphate-dithiolate ligand that binds ...

. Molybdopterin is required for all forms of life. Molybdopterin consists of a pyranopterin, a complex

heterocycle A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

featuring a

pyran In chemistry, pyran is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom and containing two double bonds. The molecular formula is C5H6O. There are two isomers of pyran that differ by the location ...

fused to a

ring. In addition, the pyran ring features two

thiolate In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...

s, which serve as

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

s in molybdo- and tungstoenzymes. In some cases, the alkyl phosphate group is replaced by an alkyl diphosphate

nucleotide Nucleotides are Organic compound, 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 o ...

. Enzymes that contain the molybdopterin cofactor include

xanthine oxidase Xanthine oxidase (XO or XAO) is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to ...

DMSO reductase DMSO reductase is a molybdenum-containing enzyme that catalyzes reduction of dimethyl sulfoxide (DMSO) to dimethyl sulfide (DMS). This enzyme serves as the terminal Oxidoreductase, reductase under anaerobic conditions in some bacteria, with DMSO b ...

sulfite oxidase Sulfite oxidase () is an enzyme in the mitochondria of all eukaryotes, with exception of the yeasts. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ...

, and

nitrate reductase Nitrate reductases are molybdoenzymes that reduce nitrate () to nitrite (). This reaction is critical for the production of protein in most crop plants, as nitrate is the predominant source of nitrogen in fertilized soils. Types Euka ...

. The only molybdenum-containing enzymes that do not feature molybdopterins are the

nitrogenase Nitrogenases are enzymes () that are produced by certain bacteria, such as cyanobacteria (blue-green bacteria) and rhizobacteria. These enzymes are responsible for the reduction of nitrogen (N2) to ammonia (NH3). Nitrogenases are the only fa ...

s (enzymes that fix nitrogen). These contain an iron-sulfur center of a very different type, which also contains molybdenum.Structure, synthesis, empirical formula for the di-sulfhydryl.
Accessed Nov. 16, 2009.

Biosynthesis

Unlike many other cofactors, molybdenum cofactor (Moco) cannot be taken up as a nutrient. The cofactor thus requires ''de novo'' biosynthesis. Molybdenum cofactor biosynthesis occurs in four steps: (i) the radical-mediated cyclization of nucleotide,

guanosine triphosphate Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only di ...

(GTP), to (8S)‑3',8‐cyclo‑7,8‑dihydroguanosine 5'‑triphosphate (), (ii) the formation of cyclic pyranopterin monophosphate (cPMP) from the , (iii) the conversion of cPMP into molybdopterin (MPT), (iv) the insertion of molybdate into MPT to form Moco. Two enzyme-mediated reactions convert

to the cyclic phosphate of pyranopterin. One of these enzymes is a

radical SAM Radical SAM enzymes belong to a superfamily of enzymes that use an iron-sulfur cluster (4Fe-4S) to reductively cleave S-Adenosyl methionine, ''S''-adenosyl-L-methionine (SAM) to generate a radical (chemistry), radical, usually a 5′-deoxyadenosyl ...

, a family of enzymes often associated with C—X bond-forming reactions (X = S, N). This intermediate pyranopterin is then converted to the molybdopterin via the action of three further enzymes. In this conversion, the enedithiolate is formed, although the substituents on sulfur remain unknown.

Sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

is conveyed from cysteinyl persulfide in a manner reminiscent of the biosynthesis of iron-sulfur proteins. The monophosphate is adenylated (coupled to ADP) in a step that activates the cofactor toward binding Mo or W. These metals are imported as their oxyanions,

molybdate In chemistry, a molybdate is a compound containing an oxyanion with molybdenum in its highest oxidation state of +6: . Molybdenum can form a very large range of such oxyanions, which can be discrete structures or polymeric extended structures, ...

, and

tungstate In chemistry, a tungstate is a Chemical compound, compound that contains an oxyanion of tungsten or is a mixed oxide containing tungsten. The simplest tungstate ion is , "orthotungstate". Many other tungstates belong to a large group of polyatomi ...

. In some enzymes, such as

, the metal is bound to one molybdopterin, whereas, in other enzymes, e.g.,

, the metal is bound to two molybdopterin cofactors. Models for the active sites of enzymes molybdopterin-containing enzymes are based on a class of ligands known as

dithiolene Dithiolene metal complexes are complexes containing 1,2-dithiolene ligands. 1,2-Dithiolene ligands, a particular case of 1,2-dichalcogenolene species along with 1,2-diselenolene derivatives, are unsaturated bidentate ligand wherein the two dono ...

Tungsten derivatives

Some bacterial oxidoreductases use

in a similar manner as

by using it in a tungsten-

complex, with molybdopterin. Thus, molybdopterin may complex with either molybdenum or tungsten. Tungsten-using enzymes typically reduce free carboxylic acids to aldehydes. The first tungsten-requiring enzyme to be discovered also requires selenium (though the precise form is unknown). In this case, the tungsten-selenium pair has been speculated to function analogously to the molybdenum-sulfur pairing of some molybdenum cofactor-requiring enzymes. Although a tungsten-containing xanthine dehydrogenase from bacteria has been found to contain tungsten-molybdopterin and ''also'' non-protein-bound selenium (thus removing the possibility of selenium in

selenocysteine Selenocysteine (symbol Sec or U, in older publications also as Se-Cys) is the 21st proteinogenic amino acid. Selenoproteins contain selenocysteine residues. Selenocysteine is an analogue of the more common cysteine with selenium in place of the ...

selenomethionine Selenomethionine (SeMet) is a naturally occurring amino acid. The L-selenomethionine enantiomer is the main form of selenium found in Brazil nuts, cereal grains, soybeans, and grassland legumes, while ''Se''-methylselenocysteine, or its γ-glu ...

form), a tungsten-selenium molybdopterin complex has not been definitively described.

Enzymes that use molybdopterin

Enzymes that use molybdopterin as cofactor or

prosthetic group 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. Not to be confused with the cosubstrate that binds to the enzyme apoenzyme (e ...

are given below. Molybdopterin is a: *Cofactor of:

, ethylbenzene dehydrogenase, glyceraldehyde-3-phosphate ferredoxin oxidoreductase, respiratory arsenate reductase,

carbon monoxide dehydrogenase In enzymology, carbon monoxide dehydrogenase (CODH) () is an enzyme that catalyzes the chemical reaction :CO + H2O + A \rightleftharpoons CO2 + AH2 The chemical process catalyzed by carbon monoxide dehydrogenase is similar to the water-gas shi ...

aldehyde oxidase Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydroxylation of some heterocycles. ...

. *Prosthetic group of:

formate dehydrogenase Formate dehydrogenases are a set of enzymes that catalyse the oxidation of formate to carbon dioxide, donating the electrons to a second substrate, such as NAD+ in formate:NAD+ oxidoreductase () or to a cytochrome in formate:ferricytochrome-b1 o ...

purine hydroxylase Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purine ...

, thiosulfate reductase.

References

{{Metabolism of vitamins, coenzymes, and cofactors Organophosphates Cofactors Pteridines Thiolates Pyrans Molybdenum Heterocyclic compounds with 3 rings

Biosynthesis

Tungsten derivatives

Enzymes that use molybdopterin

See also

References