Skip to main content
Journal cover image

Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis.

Publication ,  Journal Article
Byer, AS; Yang, H; McDaniel, EC; Kathiresan, V; Impano, S; Pagnier, A; Watts, H; Denler, C; Vagstad, AL; Piel, J; Duschene, KS; Shepard, EM ...
Published in: J Am Chem Soc
July 18, 2018

Radical S-adenosyl-l-methionine (SAM) enzymes comprise a vast superfamily catalyzing diverse reactions essential to all life through homolytic SAM cleavage to liberate the highly reactive 5'-deoxyadenosyl radical (5'-dAdo·). Our recent observation of a catalytically competent organometallic intermediate Ω that forms during reaction of the radical SAM (RS) enzyme pyruvate formate-lyase activating-enzyme (PFL-AE) was therefore quite surprising, and led to the question of its broad relevance in the superfamily. We now show that Ω in PFL-AE forms as an intermediate under a variety of mixing order conditions, suggesting it is central to catalysis in this enzyme. We further demonstrate that Ω forms in a suite of RS enzymes chosen to span the totality of superfamily reaction types, implicating Ω as essential in catalysis across the RS superfamily. Finally, EPR and electron nuclear double resonance spectroscopy establish that Ω involves an Fe-C5' bond between 5'-dAdo· and the [4Fe-4S] cluster. An analogous organometallic bond is found in the well-known adenosylcobalamin (coenzyme B12) cofactor used to initiate radical reactions via a 5'-dAdo· intermediate. Liberation of a reactive 5'-dAdo· intermediate via homolytic metal-carbon bond cleavage thus appears to be similar for Ω and coenzyme B12. However, coenzyme B12 is involved in enzymes catalyzing only a small number (∼12) of distinct reactions, whereas the RS superfamily has more than 100 000 distinct sequences and over 80 reaction types characterized to date. The appearance of Ω across the RS superfamily therefore dramatically enlarges the sphere of bio-organometallic chemistry in Nature.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

July 18, 2018

Volume

140

Issue

28

Start / End Page

8634 / 8638

Location

United States

Related Subject Headings

  • S-Adenosylmethionine
  • Protein Conformation
  • Models, Molecular
  • General Chemistry
  • Escherichia coli
  • Enzymes
  • Electron Spin Resonance Spectroscopy
  • Deoxyadenosines
  • Cobamides
  • Biocatalysis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Byer, A. S., Yang, H., McDaniel, E. C., Kathiresan, V., Impano, S., Pagnier, A., … Broderick, J. B. (2018). Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis. J Am Chem Soc, 140(28), 8634–8638. https://doi.org/10.1021/jacs.8b04061
Byer, Amanda S., Hao Yang, Elizabeth C. McDaniel, Venkatesan Kathiresan, Stella Impano, Adrien Pagnier, Hope Watts, et al. “Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis.J Am Chem Soc 140, no. 28 (July 18, 2018): 8634–38. https://doi.org/10.1021/jacs.8b04061.
Byer AS, Yang H, McDaniel EC, Kathiresan V, Impano S, Pagnier A, et al. Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis. J Am Chem Soc. 2018 Jul 18;140(28):8634–8.
Byer, Amanda S., et al. “Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis.J Am Chem Soc, vol. 140, no. 28, July 2018, pp. 8634–38. Pubmed, doi:10.1021/jacs.8b04061.
Byer AS, Yang H, McDaniel EC, Kathiresan V, Impano S, Pagnier A, Watts H, Denler C, Vagstad AL, Piel J, Duschene KS, Shepard EM, Shields TP, Scott LG, Lilla EA, Yokoyama K, Broderick WE, Hoffman BM, Broderick JB. Paradigm Shift for Radical S-Adenosyl-l-methionine Reactions: The Organometallic Intermediate Ω Is Central to Catalysis. J Am Chem Soc. 2018 Jul 18;140(28):8634–8638.
Journal cover image

Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

July 18, 2018

Volume

140

Issue

28

Start / End Page

8634 / 8638

Location

United States

Related Subject Headings

  • S-Adenosylmethionine
  • Protein Conformation
  • Models, Molecular
  • General Chemistry
  • Escherichia coli
  • Enzymes
  • Electron Spin Resonance Spectroscopy
  • Deoxyadenosines
  • Cobamides
  • Biocatalysis