Molecular insights into the biosynthesis of the F420 coenzyme

Farhad Forouhar, Mariam Abashidze, Huimin Xu, Laura L. Grochowski, Jayaraman Seetharaman, Munif Hussain, Alexandre Kuzin, Yang Chen, Weihong Zhou, Rong Xiao, Thomas B. Acton, Gaetano Montelione, Anne Galinier, Robert H. White, Liang Tong

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Coenzyme F420, a hydride carrier, is found in Archaea and some bacteria and has crucial roles in methanogenesis, antibiotic biosynthesis, DNA repair, and activation of antitubercular compounds. CofD, 2-phospho-L-lactate transferase, catalyzes the last step in the biosynthesis of F 420-0(F420 without polyglutamate), by transferring the lactyl phosphate moiety of lactyl(2)diphospho-(5′)guanosine to 7,8-didemethyl-8-hydroxy-5-deazariboflavin ribitol (Fo). CofD is highly conserved among F420-producing organisms, and weak sequence homologs are also found in non-F420-producing organisms. This superfamily does not share any recognizable sequence conservation with other proteins. Here we report the first crystal structures of CofD, the free enzyme and two ternary complexes, with Fo and Pi or with Fo and GDP, from Methanosarcina mazei. The active site is located at the C-terminal end of a Rossmann fold core, and three large insertions make significant contributions to the active site and dimer formation. The observed binding modes of Fo and GDP can explain known biochemical properties of CofD and are also supported by our binding assays. The structures provide significant molecular insights into the biosynthesis of the F420 coenzyme. Large structural differences in the active site region of the non-F420-producing CofD homologs suggest that they catalyze a different biochemical reaction.

Original languageEnglish (US)
Pages (from-to)11832-11840
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number17
DOIs
StatePublished - Apr 25 2008

Fingerprint

Biosynthesis
Catalytic Domain
Methanosarcina
Ribitol
Polyglutamic Acid
Guanosine
Archaea
Sequence Homology
Hydrides
DNA Repair
Dimers
Assays
Conservation
Bacteria
Repair
Crystal structure
Chemical activation
Phosphates
Anti-Bacterial Agents
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Cite this

Forouhar, F., Abashidze, M., Xu, H., Grochowski, L. L., Seetharaman, J., Hussain, M., ... Tong, L. (2008). Molecular insights into the biosynthesis of the F420 coenzyme. Journal of Biological Chemistry, 283(17), 11832-11840. https://doi.org/10.1074/jbc.M710352200
Forouhar, Farhad ; Abashidze, Mariam ; Xu, Huimin ; Grochowski, Laura L. ; Seetharaman, Jayaraman ; Hussain, Munif ; Kuzin, Alexandre ; Chen, Yang ; Zhou, Weihong ; Xiao, Rong ; Acton, Thomas B. ; Montelione, Gaetano ; Galinier, Anne ; White, Robert H. ; Tong, Liang. / Molecular insights into the biosynthesis of the F420 coenzyme. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 17. pp. 11832-11840.
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Forouhar, F, Abashidze, M, Xu, H, Grochowski, LL, Seetharaman, J, Hussain, M, Kuzin, A, Chen, Y, Zhou, W, Xiao, R, Acton, TB, Montelione, G, Galinier, A, White, RH & Tong, L 2008, 'Molecular insights into the biosynthesis of the F420 coenzyme', Journal of Biological Chemistry, vol. 283, no. 17, pp. 11832-11840. https://doi.org/10.1074/jbc.M710352200

Molecular insights into the biosynthesis of the F420 coenzyme. / Forouhar, Farhad; Abashidze, Mariam; Xu, Huimin; Grochowski, Laura L.; Seetharaman, Jayaraman; Hussain, Munif; Kuzin, Alexandre; Chen, Yang; Zhou, Weihong; Xiao, Rong; Acton, Thomas B.; Montelione, Gaetano; Galinier, Anne; White, Robert H.; Tong, Liang.

In: Journal of Biological Chemistry, Vol. 283, No. 17, 25.04.2008, p. 11832-11840.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular insights into the biosynthesis of the F420 coenzyme

AU - Forouhar, Farhad

AU - Abashidze, Mariam

AU - Xu, Huimin

AU - Grochowski, Laura L.

AU - Seetharaman, Jayaraman

AU - Hussain, Munif

AU - Kuzin, Alexandre

AU - Chen, Yang

AU - Zhou, Weihong

AU - Xiao, Rong

AU - Acton, Thomas B.

AU - Montelione, Gaetano

AU - Galinier, Anne

AU - White, Robert H.

AU - Tong, Liang

PY - 2008/4/25

Y1 - 2008/4/25

N2 - Coenzyme F420, a hydride carrier, is found in Archaea and some bacteria and has crucial roles in methanogenesis, antibiotic biosynthesis, DNA repair, and activation of antitubercular compounds. CofD, 2-phospho-L-lactate transferase, catalyzes the last step in the biosynthesis of F 420-0(F420 without polyglutamate), by transferring the lactyl phosphate moiety of lactyl(2)diphospho-(5′)guanosine to 7,8-didemethyl-8-hydroxy-5-deazariboflavin ribitol (Fo). CofD is highly conserved among F420-producing organisms, and weak sequence homologs are also found in non-F420-producing organisms. This superfamily does not share any recognizable sequence conservation with other proteins. Here we report the first crystal structures of CofD, the free enzyme and two ternary complexes, with Fo and Pi or with Fo and GDP, from Methanosarcina mazei. The active site is located at the C-terminal end of a Rossmann fold core, and three large insertions make significant contributions to the active site and dimer formation. The observed binding modes of Fo and GDP can explain known biochemical properties of CofD and are also supported by our binding assays. The structures provide significant molecular insights into the biosynthesis of the F420 coenzyme. Large structural differences in the active site region of the non-F420-producing CofD homologs suggest that they catalyze a different biochemical reaction.

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Forouhar F, Abashidze M, Xu H, Grochowski LL, Seetharaman J, Hussain M et al. Molecular insights into the biosynthesis of the F420 coenzyme. Journal of Biological Chemistry. 2008 Apr 25;283(17):11832-11840. https://doi.org/10.1074/jbc.M710352200