In enzymology, histidinol dehydrogenase (HIS4) (HDH) () is an

enzyme 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 ...

that catalyzes the

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

:L-histidinol + 2 NAD⁺

\rightleftharpoons

L-histidine + 2 NADH + 2 H⁺ Thus, the two substrates of this enzyme are L-histidinol and NAD⁺, whereas its 3

products Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produ ...

are L-histidine,

NADH 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 aden ...

, and H⁺. This enzyme belongs to the family of

oxidoreductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually u ...

s, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

of this enzyme class is L-histidinol:NAD⁺ oxidoreductase. This enzyme is also called L-histidinol dehydrogenase. Histidinol dehydrogenase catalyzes the terminal step in the biosynthesis of

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

, and

plants Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclude ...

, the four-

electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no ...

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

of L-histidinol to histidine. In 4-electron dehydrogenases, a single active site catalyses 2 separate

steps: oxidation of the substrate alcohol to an intermediate

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

; and oxidation of the aldehyde to the

product Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produ ...

acid, in this case His. The reaction proceeds via a tightly- or covalently-bound inter-mediate, and requires the presence of 2 NAD

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

s. By contrast with most dehydrogenases, the substrate is bound before the NAD

coenzyme 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 ass ...

. A Cys residue has been implicated in the catalytic mechanism of the second oxidative step. In bacteria HDH is a single chain polypeptide; in

it is the C-terminal domain of a multifunctional

which

catalyse Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

s three different steps of histidine biosynthesis; and in

it is expressed as a nuclear encoded

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...

which is exported to the chloroplast.

Co-regulation of the gene

Histodinol dehydrogenase gene (''HIS4'') has been shown co-regulating the adjacent gene while it is under amino acids

selective pressure Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...

Structural studies

As of late 2007, 4

structures A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

have been solved for this class of enzymes, with PDB accession codes , , , and .

Co-regulation of the gene

Structural studies

References

Further reading