A hydrogenase is an 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...

 that catalyses

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 the reversible oxidation

Redox

Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 of molecular hydrogen

Hydrogen

Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

 (H₂). Hydrogenases play a vital role in anaerobic metabolism

Glycolysis

Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...

.

Hydrogen uptake (H₂ oxidation) (1) is coupled to the reduction of electron acceptors such as oxygen

Oxygen

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

, nitrate

Nitrate

The nitrate ion is a polyatomic ion with the molecular formula NO and a molecular mass of 62.0049 g/mol. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identically-bonded oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a...

, sulfate

Sulfate

In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...

, carbon dioxide

Carbon dioxide

Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

, and fumarate, whereas proton reduction (H₂ evolution) (2) is essential in pyruvate fermentation and in the disposal of excess electrons. Both low-molecular weight compounds and proteins such as ferredoxin

Ferredoxin

Ferredoxins are iron-sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co...

s, cytochrome

Cytochrome

Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport.They are found either as monomeric proteins or as subunits of bigger enzymatic complexes that catalyze redox reactions....

 c₃, and cytochrome c₆ can act as physiological electron donors (D) or acceptors (A) for hydrogenases:

H₂ + A_ox → 2H⁺ + A_red (1)

2H⁺ + D_red → H₂ + D_ox (2)

Hydrogenases were first discovered in the 1930s, and they have since attracted interest from many researchers including inorganic chemists

Inorganic chemistry

Inorganic chemistry is the branch of chemistry concerned with the properties and behavior of inorganic compounds. This field covers all chemical compounds except the myriad organic compounds , which are the subjects of organic chemistry...

 who have synthesized a variety of hydrogenase mimic

Hydrogenase mimic

-Overview:The fields of molecular biology and inorganic chemistry overlap in the study of metalloenzymes in the form of enzyme mimics among other. The advantage of indirect modeling or enzyme mimicry is high-resolution crystal structures and well-defined spectral data from which comparisons can be...

s. Understanding the catalytic mechanism of hydrogenase might help scientists design clean biological energy sources, such as algae, that produce hydrogen.http://www.wired.com/news/technology/0,70273-0.html?tw=rss.index.

Biochemical classification

EC

EC number

The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze....

 1.2.1.2 http://enzyme.expasy.org/EC/1.2.1.2 hydrogen dehydrogenase

Hydrogen dehydrogenase

In enzymology, a hydrogen dehydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are H2 and NAD+, whereas its two products are H+ and NADH....

 (hydrogen:NAD⁺ oxidoreductase)

H₂ + NAD⁺ = H⁺ + NADH

EC 1.12.1.3
hydrogen dehydrogenase (NADP) (hydrogen:NADPH⁺ oxidoreductase)

H₂ + NADP⁺ = H⁺ + NADPH

EC 1.12.2.1
cytochrome-c₃ hydrogenase

Cytochrome-c3 hydrogenase

In enzymology, a cytochrome-c3 hydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are H2 and ferricytochrome c3, whereas its two products are H+ and ferrocytochrome c3....

 (hydrogen:ferricytochrome-c₃ oxidoreductase)

2H₂ + ferricytochrome c₃ = 4H⁺ + ferrocytochrome c₃

EC 1.12.7.2
ferredoxin hydrogenase

Ferredoxin hydrogenase

In enzymology, a ferredoxin hydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are H2 and oxidized ferredoxin, whereas its two products are reduced ferredoxin and H+....

 (hydrogen:ferredoxin oxidoreductase)

H₂ + oxidized ferredoxin = 2H⁺ + reduced ferredoxin

EC 1.12.98.1
coenzyme F₄₂₀ hydrogenase

Coenzyme F420 hydrogenase

In enzymology, a coenzyme F420 hydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are H2 and coenzyme F420, whereas its product is reduced coenzyme F420....

 (hydrogen:coenzyme F₄₂₀ oxidoreductase)

H₂ + coenzyme F₄₂₀ = reduced coenzyme F₄₂₀

EC 1.12.99.6
hydrogenase (acceptor) (hydrogen:acceptor oxidoreductase)

H₂ + A = AH₂

EC 1.12.5.1
hydrogen:quinone oxidoreductase

H₂ + menaquinone = menaquinol

EC 1.12.98.2
5,10-methenyltetrahydromethanopterin hydrogenase (hydrogen:5,10-methenyltetrahydromethanopterin oxidoreductase)

H₂ + 5,10-methenyltetrahydromethanopterin = H⁺ + 5,10-methylenetetrahydromethanopterin

EC 1.12.98.3
Methanosarcina-phenazine hydrogenase [hydrogen:2-(2,3-dihydropentaprenyloxy)phenazine oxidoreductase]

H₂ + 2-(2,3-dihydropentaprenyloxy)phenazine = 2-dihydropentaprenyloxyphenazine

Structural classification

Until 2004, hydrogenases were classified according to the metals thought to be at their active sites; three classes were recognized: iron-only ([FeFe]), nickel-iron ([NiFe]), and "metal-free". In 2004, Thauer et al. showed that the metal-free hydrogenases in fact contain iron. Thus, those enzymes previously called "metal-free" are now named [Fe]-hydrogenases, since this protein contains only a mononuclear Fe active site and no iron-sulfur clusters, in contrast to the [FeFe]-enzymes. In some [NiFe]-hydrogenases, one of the Ni-bound cysteine residues is replaced by selenocysteine

Selenocysteine

Selenocysteine is an amino acid that is present in several enzymes .-Nomenclature:...

. On the basis of sequence similarity, however, the [NiFe]- and [NiFeSe]-hydrogenases should be considered a single superfamily.

• The [NiFe]-hydrogenases are heterodimeric proteins consisting of small (S) and large (L) subunits. The small subunit contains three iron-sulfur cluster
  Iron-sulfur cluster
  For biological Fe-S clusters, see iron-sulfur proteins.Iron-sulfur clusters are ensembles of iron and sulfide centres. Fe-S clusters are most often discussed in the context of the biological role for iron-sulfur proteins. Many Fe-S clusters are known in the area of organometallic chemistry and as...
  
  s while the large subunit contains the active site, a nickel-iron centre which is connected to the solvent by a molecular tunnel. Periplasmic, cytoplasmic, and cytoplasmic membrane-bound hydrogenases have been found. The [NiFe]-hydrogenases, when isolated, are found to catalyse both H₂ evolution and uptake, with low-potential multihaem cytochromes such as cytochrome c₃ acting as either electron donors or acceptors, depending on their oxidation state.

• • The novel [NiFe] hydrogenases of Ralstonia eutropha
    Ralstonia eutropha
    Ralstonia eutropha is a gram-negative soil bacterium of the betaproteobacteria class.-Taxonomy:R. eutropha has gone through a series of name changes. In the first half of the 20th century many microorganisms were isolated for their ability to utilize hydrogen. Hydrogen metabolizing...
    
    are unlike typical [NiFe] hydrogenases because they are tolerant to oxygen and carbon monoxide.

• The hydrogenases containing Fe-S clusters and no metal other than iron are called [FeFe]-hydrogenases ([FeFe]-H₂ases). Three families of [FeFe]-H₂ases are recognized:

• • (I) cytoplasmic, soluble, monomeric [FeFe]-H₂ases, found in strict anaerobes such as Clostridium pasteurianum and Megasphaera elsdenii. They are extremely sensitive to inactivation by dioxygen (O₂) and catalyse both H₂ evolution and uptake.

• • (II) periplasmic, heterodimeric [FeFe]-H₂ases from Desulfovibrio spp., which can be purified aerobically and catalyse mainly H₂ oxidation.

• • (III) soluble, monomeric [FeFe]-H₂ases, found in chloroplasts of green alga Scenedesmus obliquus, catalyses H₂ evolution. The [Fe₂S₂] ferredoxin functions as natural electron donor linking the enzyme to the photosynthetic electron transport chain.

[NiFe]- and [FeFe]-hydrogenases have some common features in their structures: each enzyme has an active site and a few Fe-S clusters that are buried in protein. The active site, which is believed to be the place where catalysis takes place, is also a metallocluster, and each metal is coordinated by carbon monoxide

Carbon monoxide

Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...

 (CO) and cyanide

Cyanide

A cyanide is a chemical compound that contains the cyano group, -C≡N, which consists of a carbon atom triple-bonded to a nitrogen atom. Cyanides most commonly refer to salts of the anion CN−. Most cyanides are highly toxic....

 (CN^-) ligands.

• 5,10-methenyltetrahydromethanopterin hydrogenase
  5,10-methenyltetrahydromethanopterin hydrogenase
  The 5,10-methenyltetrahydromethanopterin hydrogenase , the so-called iron-sulfur cluster-free hydrogenase, is an enzyme found in methanogenic archea such as Methanothermacter marburgensis. It was discovered and first characterized by the Thauer group at the Max Planck Institute in Marburg...
  
   (EC 1.12.98.2) found in methanogen
  Methanogen
  Methanogens are microorganisms that produce methane as a metabolic byproduct in anoxic conditions. They are classified as archaea, a group quite distinct from bacteria...
  
  ic Archaea
  Archaea
  The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
  
   contains neither nickel nor iron-sulfur clusters but an iron-containing cofactor that was recently characterized by X-ray diffraction.

External links

• 2B0J - PDB
  Protein Data Bank
  The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
  
   Structure of the Apoenzyme of the Iron-sulphur cluster-free hydrogenase from Methanothermococcus jannaschii
• 1HFE - PDB
  Protein Data Bank
  The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
  
  structure of [FeFe]-hydrogenase from Desulfovibrio desulfuricans
• 1C4A - PDB structure of [FeFe]-hydrogenase from Clostridium pasteurianum
• 1UBR - PDB structure of [NiFe]-hydrogenase from Desulfovibrio vulgaris
• 1CC1 - PDB structure of [NiFeSe]-hydrogenase from Desulfomicrobium baculatum
• Animation - Mechanism of [NiFe]-hydrogenase