Flavodoxins (Fld) are small, soluble electron-transfer

proteins 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, respondi ...

. Flavodoxins contains

flavin mononucleotide Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, a ...

as prosthetic group. The structure of flavodoxin is characterized by a five-stranded parallel

beta sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

, surrounded by five

alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earli ...

. They have been isolated from

prokaryotes A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Conn ...

, cyanobacteria, and some eukaryotic

algae Algae ( , ; : alga ) are any of a large and diverse group of photosynthetic, eukaryotic organisms. The name is an informal term for a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from ...

Background

Originally found in cyanobacteria and

clostridia The Clostridia are a highly polyphyletic class of Bacillota, including '' Clostridium'' and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. S ...

, flavodoxins were discovered over 50 years ago. These proteins evolved from an anaerobic environment, due to selective pressures.

Ferredoxin Ferredoxins (from Latin ''ferrum'': iron + redox, often abbreviated "fd") 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. and applied ...

, another redox protein, was the only protein able to be used in this manner. However, when oxygen became present in the environment,

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...

became limited. Ferredoxin is iron-dependant as well as oxidant-sensitive. Under these limited iron conditions, ferredoxin was no longer preferred. Flavodoxin on the other hand is the opposite of these traits, as it is oxidant-resistant and has iron-free isofunctional counterparts. Therefore, for some time flavodoxin was the primary redox protein. Now however, when ferredoxin and flavodoxin are present in the same

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...

, ferredoxin is still used but under low iron conditions, flavodoxin is induced.

Structure

Three forms of flavodoxin exist:

Oxidized 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 de ...

, (OX)

semiquinone Semiquinone (or ubisemiquinone) is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone, such as hydroquinone itself or catechol, to a quinone or alternatively the ...

, (SQ) and

hydroquinone Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''para'' ...

(HQ). While relatively small (M_w = 15-22 kDa), flavodoxins exist in "long" and "short" chain classifications. Short chain flavodoxins contain between 140 and 180 amino acid residues, while long chain flavodoxins include a 20

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

insertion into the last

beta-strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

. These residues form a loop which may be used to increase the

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mo ...

of flavin mononucleotide as well as assist in the formation of folded intermediates. However, it is still not certain what the loops true function is. In addition, the flavin mononucleotide is non-covalently bound to the flavodoxin protein and works to shuttle

electron The electron (, or in nuclear reactions) 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 partic ...

Medical applications

'' Heliobacter pylori (Hp),'' the most prevalent human gastric pathogen, requires flavodoxins in its essential POR (pyruvate oxidoreductase enzyme complex) used in pyruvate decarboxylation. Most flavodoxins have a large hydrophobic residue such as tryptophan near the FMN, but ''Hp'' has an alanine residue instead, allowing for a pocket of solute to form. Current research is being done to identify non toxic, ''Hp'' specific flavodoxin inhibitors for the purpose of treating infection.

Mechanism

Flavodoxins require a highly negative redox potential to be active. The semiquinone conformation is stabilized by a hydrogen bond to the N-5 position of the flavin. This bond, as well as a common

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromati ...

residue near the binding site, aid in lowering SQ reactivity. The hydroquinone form is forced into a planar conformation, destabilizing it. Electron transfer occurs at the dimethylbenzene ring of the FMN.

Flavodoxins in Cyanobacteria

In cyanobacteria such as ''Nostoc'' ''sp''., flavodoxins are

heterocyst Heterocysts or heterocytes are specialized nitrogen-fixing cells formed during nitrogen starvation by some filamentous cyanobacteria, such as '' Nostoc punctiforme'', ''Cylindrospermum stagnale'', and ''Anabaena sphaerica''. They fix nitrogen fro ...

-specific, and used in

photosystem 1 Photosystem I (PSI, or plastocyanin–ferredoxin oxidoreductase) is one of two photosystems in the photosynthetic light reactions of algae, plants, and cyanobacteria. Photosystem I is an integral membrane protein complex that use ...

to deliver electrons to nitrogenase, as well as reducing N2 and NADP+, nitrogen fixation and H2 formation.

References

External links

*
"Flavodoxin Folding and Stability Research at Wageningen University, the Netherlands"

{{Flavoproteins Proteins Bacteria