Molybdopterin
Encyclopedia
Molybdopterins, when reacted with molybdenum or tungsten in the form of molybdate or tungstate, are a class of cofactors
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

 found in most molybdenum
Molybdenum
Molybdenum , is a Group 6 chemical element with the symbol Mo and atomic number 42. The name is from Neo-Latin Molybdaenum, from Ancient Greek , meaning lead, itself proposed as a loanword from Anatolian Luvian and Lydian languages, since its ores were confused with lead ores...

 (Mo) and all tungsten
Tungsten
Tungsten , also known as wolfram , is a chemical element with the chemical symbol W and atomic number 74.A hard, rare metal under standard conditions when uncombined, tungsten is found naturally on Earth only in chemical compounds. It was identified as a new element in 1781, and first isolated as...

 (W) enzymes. Synonyms for molydopterin are: MPT and pyranopterin-dithiolate.

The nomenclature for this biomolecule can be confusing: molybdopterin per se contains no molybdenum; rather, this is the name of the ligand that will eventually bind the active metal. After molydopterin is eventually complexed with molybdate, the complete ligand is usually called molybdenum cofactor
Molybdenum cofactor
Molybdenum cofactor is a cofactor required for the activity of enzymes such as sulfite oxidase, xanthine oxidoreductase, and aldehyde oxidase. It is a coordination complex formed between molybdopterin and an oxide of molybdenum.Molybdopterins, in turn, are synthesized from guanosine triphosphate...

.

Molydopterin consists of a pyranopterin, a complex heterocycle featuring a pyran
Pyran
In chemistry, a pyran, or oxine, 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 of the double bonds...

 fused to a pterin
Pterin
Pterin is a heterocyclic compound composed of a pteridine ring system, with a keto group and an amino group on positions 4 and 2 respectively...

 ring. In addition, the pyran ring features two thiolates, which serve as ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s in molybdo- and tungstoenzymes. In some cases, the alkyl phosphate group is replaced by an alkyl diphosphate nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

. Enzymes that contain the molybdopterin cofactor include xanthine oxidase
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...

, DMSO reductase
DMSO reductase
DMSO reductase is a molybdenum-containing enzyme capable of reducing dimethyl sulfoxide to dimethyl sulfide . This enzyme serves as the terminal reductase under anaerobic conditions in some bacteria, with DMSO being the terminal electron acceptor...

, sulfite oxidase
Sulfite oxidase
Sulfite oxidase is an enzyme in the mitochondria of all eukaryotes. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation...

, and nitrate reductase
Nitrate reductase
Nitrate reductases are molybdoenzymes that reduce nitrate to nitrite .* Eukaryotic nitrate reductases are part of the sulfite oxidase family of molybdoenzymes....

.

The only molybdenum-containing enzymes that do not feature molydopterins are the nitrogenase
Nitrogenase
Nitrogenases are enzymes used by some organisms to fix atmospheric nitrogen gas . It is the only known family of enzymes that accomplish this process. Dinitrogen is quite inert because of the strength of its N-N triple bond...

s (enzymes that fix nitrogen). These contain an iron-sulfur center of a very different type, which also usually contains molybdenum. However, if molybdenum is present, it is directly bonded to other metal atoms.

Biosynthesis

The biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 of molybdopterin begins with guanosine
Guanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...

 triphosphate. Two enzymatic reactions convert this triphosphate to the cyclic phosphate of pyranopterin. One of these enzymes utilizes radical SAMs, often associated with C—X bond-forming reactions. 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
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

 is conveyed from cysteinyl persulfide in a manner reminiscent of the biosynthesis of iron-sulfur protein
Iron-sulfur protein
Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states...

s. 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
Molybdate
In chemistry a molybdate is a compound containing an oxoanion with molybdenum in its highest oxidation state of 6. Molybdenum can form a very large range of such oxoanions which can be discrete structures or polymeric extended structures, although the latter are only found in the solid state.The...

, and tungstate
Tungstate
In chemistry a tungstate is a compound that contains an oxoanion of tungsten or is a mixed oxide containing tungsten. The simplest tungstate ion is WO42−, "orthotungstate"...

. Finally, Mo or W is inserted to give the molybdopterin cofactor. In some enzymes, such as xanthine oxidase
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...

, the metal is bound to one molybdopterin, whereas, in other enzymes, e.g., DMSO reductase
DMSO reductase
DMSO reductase is a molybdenum-containing enzyme capable of reducing dimethyl sulfoxide to dimethyl sulfide . This enzyme serves as the terminal reductase under anaerobic conditions in some bacteria, with DMSO being the terminal electron acceptor...

, 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 dithiolene complexes are complexes containing dithiolene ligands. Dithiolene ligands are unsaturated bidentate ligand wherein the two donor atoms are sulfur. Dithiolenes are often referred to as "metallodithiolenes" or "dithiolene complexes"...

s.

Selenium-containing version, and ability to bind active tungsten

Tungsten has not been found to be necessary or used in eukaryotes, but it is an essential nutrient
Essential nutrient
An essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health , and thus must be obtained from a dietary source...

 for some bacteria. For example, enzyme
Enzyme
Enzymes 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...

s called oxidoreductase
Oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...

s use tungsten in a similar manner as molybdenum
Molybdenum
Molybdenum , is a Group 6 chemical element with the symbol Mo and atomic number 42. The name is from Neo-Latin Molybdaenum, from Ancient Greek , meaning lead, itself proposed as a loanword from Anatolian Luvian and Lydian languages, since its ores were confused with lead ores...

 by using it in a tungsten-pterin
Pterin
Pterin is a heterocyclic compound composed of a pteridine ring system, with a keto group and an amino group on positions 4 and 2 respectively...

 complex with molybdopterin. Thus, molybdopterin may complex with either molybdenum or tungsten in use by bacteria. Tungsten-using enzymes typically reduce free carboxylic acids to aldehydes. The first tungsten-requiring enzyme to be discovered also requires selenium, and in this case the tungsten-selenium pair may function analogously to the molybdenum-sulfur pairing of some molybdenum cofactor
Molybdenum cofactor
Molybdenum cofactor is a cofactor required for the activity of enzymes such as sulfite oxidase, xanthine oxidoreductase, and aldehyde oxidase. It is a coordination complex formed between molybdopterin and an oxide of molybdenum.Molybdopterins, in turn, are synthesized from guanosine triphosphate...

-requiring enzymes. One of the enzymes in the oxidoreductase family which sometimes employ tungsten (bacterial formate dehydrogenase
Formate dehydrogenase
Formate dehydrogenases are a set of enzymes that catalyse the oxidation of formate to bicarbonate, donating the electrons to a second substrate, such as NAD+ in formate:NAD+ oxidoreductase or to a cytochrome in formate:ferricytochrome-b1 oxidoreductase .-Biological function:NAD-dependent formate...

 H) is known to use a selenium-molybdenum version of molybdopterin. Although a tungsten-containing xanthine dehydrogenase from bacteria has been found to contain tungsten-molydopterin and also non-protein bound selenium, a tungsten-selenium molybdopterin complex has not been definitively described.

Enzymes that use molydopterin

Enzymes that use molydopterin as cofactor or prosthetic group:
Cofactor of: xanthine oxidase
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...

, DMSO reductase
DMSO reductase
DMSO reductase is a molybdenum-containing enzyme capable of reducing dimethyl sulfoxide to dimethyl sulfide . This enzyme serves as the terminal reductase under anaerobic conditions in some bacteria, with DMSO being the terminal electron acceptor...

, sulfite oxidase
Sulfite oxidase
Sulfite oxidase is an enzyme in the mitochondria of all eukaryotes. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation...

, nitrate reductase
Nitrate reductase
Nitrate reductases are molybdoenzymes that reduce nitrate to nitrite .* Eukaryotic nitrate reductases are part of the sulfite oxidase family of molybdoenzymes....

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

Prosthetic group of: formate dehydrogenase
Formate dehydrogenase
Formate dehydrogenases are a set of enzymes that catalyse the oxidation of formate to bicarbonate, donating the electrons to a second substrate, such as NAD+ in formate:NAD+ oxidoreductase or to a cytochrome in formate:ferricytochrome-b1 oxidoreductase .-Biological function:NAD-dependent formate...

, purine hydroxylase, thiosulfate reductase.
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