F420

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Structural formula
Structure of F420
General
Surname F420
other names
  • Coenzyme F 420
  • N - ( N - { O - [5- (8-Hydroxy-2,4-dioxo-2,3,4,10-tetra-hydropyrimido [4,5- b ] quinolin-10-yl) -5-deoxy) - L -ribityl-1-phospho] - ( S ) -lactyl} -γ- L -glutamyl) - L -glutamate
Molecular formula C 29 H 32 N 5 O 18 P 4−
External identifiers / databases
CAS number 64885-97-8
EC number 613-724-2
ECHA InfoCard 100.110.762
PubChem 123996
ChemSpider 110515
DrugBank DB03913
Wikidata Q412727
properties
Molar mass 769.6 g mol −1
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

F 420 is a cofactor , a chemical compound that occurs in the cytoplasm of methanogenic archaea , some bacteria and unicellular eukaryotes . It is biochemically an electron transporter , and chemically it is deaza flavine , similar to riboflavin . They differ in the length of the polyglutamate chain, which in the mycobacteria contains five to seven Glu residues. A member of the group was first isolated in 1972. The chemical structure was clarified in 1978. The cofactor owes its name to its strong light absorption at a wavelength λ max  = 420 nm.

Optical properties

Oxidized F 420 absorbs at 420 nm, after absorption light is emitted at 520 nm. At the isosbestic point at 401 nm, the cofactor has an extinction coefficient of 25.9 mM −1 cm −1 . After reduction (F 420 H 2 ), F 420 loses its absorption maximum at 420 nm and this shifts to 320 nm, but with a lower extinction coefficient.

Biological importance

F 420 has a similar structure to riboflavin or FAD , but chemically it is more similar to nicotinamides, such as. B. NADP + . The redox potential of F 420 is −350 mV and therefore resembles that of es NAD (P) s (−320 mV). F 420 transfers only one hydride ion (two electrons and one proton) - like NAD + or NADP + .

The basic structure, the 7,8-didemethyl-8-hydroxy-5-deazariboflavin-5'-phosphate, occurs in archaea, but also in gram-positive eubacteria such as Streptomyces or Mycobacteria . The cofactor was also discovered in the cyanobacterium Anacystis nidulans and in the (eukaryotic) green alga Scenedesmus acutus . However, the basic structure varies in those organisms.

F 420 is involved in processes of methanogenesis , sulphite reduction, oxygen detoxification and electron transport in archaea.

It is a cofactor in the synthesis of antibiotics in streptomycetes and for the reduction of nitrogen dioxide and PA-824 in mycobacteria , where it is reduced again by glucose-6-phosphate dehydrogenase . PA-824 is an experimental drug used to treat tuberculosis.

F420-dependent enzymes

F 420 is often used as an electron carrier in methanogenesis, but it also appears in other processes:

Tetrahydromethanopterin-dependent enzyme

During methanogenesis - starting from CO 2 - tetrahydromethanopterin-dependent enzymes play a central role. The F 420 -dependent N 5 , N 10 -methylene tetrahydromethanopterin dehydrogenase reduces methenyl bound to methanopterin to methylene. (Reduced) F 420 H 2 is consumed in the process (cf. equation 1).

The F 420 -dependent N 5 , N 10 -methylene tetrahydromethanopterin reductase reduces the methylene bound to methanopterin further to methyl with consumption of F 420 H 2 (see equation 2):

F420 reducing hydrogenase

An enzyme is required for the regeneration of oxidized F 420 , which is called F 420 -reducing hydrogenase. The enzyme is either frequently membrane-bound or occasionally also localized in the cytoplasm.

NADP / F420 oxidoreductase

The transfer of 2 reducing equivalents from F 420 H 2 to NADP + is catalyzed by a transhydrogenase, an NADP / F 420 oxidoreductase. NADPH itself is required in methanogenic bacteria for the synthesis of certain cellular metabolites, but also in NADPH-dependent alcohol dehydrogenases .

Formate dehydrogenease

Some methanogenic organisms can obtain reduction equivalents through the oxidation of formic acid . Since the oxidation goes hand in hand with the reduction of F 420 , F 420 is regenerated again. This enzyme has already been purified in Methanobacterium formicicum and expressed in E. coli .

Alcohol dehydrogenase

Isopropanol and ethanol are used by various methanogenic organisms as an alternative source of electrons for the reduction of CO 2 . In methanogenic archaea, for example, isopropanol is oxidized to acetone by an F 420 -dependent secondary alcohol dehydrogenase with consumption of reduced F 420 .

Pharmacological importance

An in silico screening for F420-dependent enzymes revealed a surprisingly high number of candidates in M. tuberculosis . Although these enzymes have not yet been characterized biochemically, they could represent a pharmacological target , since there are almost no bacteria with such enzymes in the intestinal flora, and antibiotics against M. tuberculosis based on the inhibition of F420-dependent enzymes therefore hardly have any side effects on the Intestinal flora.

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  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ Cheeseman, P. et al. (1972): Isolation and properties of a fluorescent compound, factor 420, from Methanobacterium strain MoH In: J Bacteriol. 112 (1); 527-31; PMID 5079072 ; PDF (free full text access)
  3. ↑ a b Eirich, LD. et al. (1978): Proposed structure for coenzyme F420 from Methanobacterium . In: Biochemistry 17 (22); 4583-93; PMID 728375
  4. ↑ G. Bashiri, CJ Squire, NJ Moreland, EN Baker: Crystal structures of F420-dependent glucose-6-phosphate dehydrogenase FGD1 involved in the activation of the anti-tuberculosis drug candidate PA-824 reveal the basis of coenzyme and substrate binding. In: The Journal of biological chemistry . Volume 283, Number 25, June 2008, pp. 17531-17541. doi : 10.1074 / jbc.M801854200 . PMID 18434308 .
  5. ^ DiMarco AA. et al. (1990): Unusual coenzymes of methanogenesis . In: Annu Rev Biochem . 59 ; 355-94; PMID 2115763
  6. ↑ Jacobson, F. and Walsh, C. (1984): Properties of 7,8-didemethyl-8-hydroxy-5-deazaflavins relevant to redox coenzyme function in methanogen metabolism . In: Biochemistry 23 ; 979-988
  7. ^ McCormick, JRD. and George O. Morton, GO. (1982): Identity of cosynthetic factor I of Streptomyces aureofaciens and fragment FO from coenzyme F420 of Methanobacterium species . In: J. Am. Chem. Soc. 104 (14); 4014-4015; doi : 10.1021 / ja00378a044
  8. ↑ Eker, AP. et al. (1990): DNA photoreactivating enzyme from the cyanobacterium Anacystis nidulans . In: J Biol Chem. 265 (14); 8009-15; PMID 2110564 ; PDF (free full text access)
  9. ↑ Eker, AP. et al. (1998): Photo-reactivating enzyme from the green alga Scenedesmus acutus. Evidence for two different chromophores . In: Biochemistry 27 (5); 1758-1765; doi : 10.1021 / bi00405a056
  10. ^ Graham, DE. and White, RH. (2002): Elucidation of methanogenic coenzyme biosyntheses: from spectroscopy to genomics . In: Nat Prod Rep . 19 (2); 133-47; PMID 12013276
  11. ^ Johnson, EF. and Mukhopadhyay, B. (2005): A new type of sulfite reductase, a novel coenzyme F420-dependent enzyme, from the methanarchaeon Methanocaldococcus jannaschii. In: J Biol Chem. 2005 280 (46); 38776-86; PMID 16048999 ; PDF (free full text access)
  12. ↑ Seedorf, H. et al. (2004): F420H2 oxidase (FprA) from Methanobrevibacter arboriphilus, a coenzyme F420-dependent enzyme involved in O2 detoxification . In: Arch Microbiol. 182 (2-3); 126-37; PMID 15340796
  13. ↑ Deppenmeier U. (2004): The membrane-bound electron transport system of Methanosarcina species . In: J Bioenerg Biomembr. 36 (1); 55-64; PMID 15168610
  14. ↑ Daniels, L, Bakhiet, N, Harmon, K: Widespread distribution of a 5-deazaflavin cofactor in Actinomyces and related bacteria. In: Syst. Appl. Microbiol. Vol. 6, no. 1, pp. 12-17. 1985.
  15. ↑ E. Purwantini, B. Mukhopadhyay: Conversion of NO2 to NO by reduced coenzyme F420 protects mycobacteria from nitrosative damage. In: Proceedings of the National Academy of Sciences Volume 106, Number 15, April 2009, pp. 6333-6338. doi : 10.1073 / pnas.0812883106 . PMID 19325122 . PMC 266939 (free full text).
  16. ↑ UH Manjunatha, H. Boshoff u. a .: Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. In: Proceedings of the National Academy of Sciences Volume 103, Number 2, January 2006, pp. 431-436. doi : 10.1073 / pnas.0508392103 . PMID 16387854 .
  17. ↑ EC number 1.5.99.9 (methylene tetrahydromethanopterin dehydrogenase)
  18. ↑ te Brömmelstroet, BW. et al. (1991): Purification and properties of 5,10-methylenetetrahydromethanopterin dehydrogenase and 5,10-methylenetetrahydromethanopterin reductase, two coenzyme F420-dependent enzymes, from Methanosarcina barkeri . In: Biochim Biophys Acta . 1079 (3); 293-302; PMID 1911853
  19. ↑ Hagemeier, CH. et al. (2003): Coenzyme F420-dependent methylenetetrahydromethanopterin dehydrogenase (Mtd) from Methanopyrus kandleri: a methanogenic enzyme with an unusual quaternary structure . In: J Mol Biol. 332 (5); 1047-1057; PMID 14499608
  20. ↑ EC number 1.5.99.11 (methylene tetrahydromethanopterin reductase)
  21. ↑ EC number 1.12.98.1 (F 420 -reducing hydrogenase)
  22. ↑ Fox, YES. et al. (1987): 8-Hydroxy-5-deazaflavin-reducing hydrogenase from Methanobacterium thermoautotrophicum: 1. Purification and characterization . In: Biochemistry 26 (14); 4219-27; PMID 3663585
  23. ↑ Deppenmeier, U. (2002): The Unique Biochemistry of Methanogenesis . In: Prog Nucleic Acid Res Mol Biol. 71 ; 223-83; PMID 12102556
  24. ↑ Yamazaki, S. and Tsai, L. (1980): Purification and properties of 8-hydroxy-5-deazaflavin-dependent NADP + reductase from Methanococcus vannielii . In: J Biol Chem. 255 (13); 6462-5; PMID 7391030 ; PDF (free full text access)
  25. ↑ Berk, H. and Thauer RK. (1997): Function of coenzyme F420-dependent NADP reductase in methanogenic archaea containing an NADP-dependent alcohol dehydrogenase . In: Arch Microbiol. 168 (5); 396-402; PMID 9325428
  26. ↑ Shuber, AP. et al. (1986): Cloning, expression, and nucleotide sequence of the formate dehydrogenase genes from Methanobacterium formicicum . In: J Biol Chem. 261 (28); 12942-7; PMID 3531194 ; PDF (free full text access)
  27. Jump up ↑ SW. et al. (2004): Coenzyme binding in F420-dependent secondary alcohol dehydrogenase, a member of the bacterial luciferase family . In: Structure 12 (3); 361-70; PMID 15016352
  28. ↑ JD Selengut, DH Haft: Unexpected abundance of coenzyme F (420) -dependent enzymes in Mycobacterium tuberculosis and other actinobacteria. In: Journal of bacteriology. Volume 192, Number 21, November 2010, pp. 5788-5798, doi : 10.1128 / JB.00425-10 . PMID 20675471 . PMC 2953692 (free full text).

literature

See also