A radical intermediate in tyrosine scission to the CO and CN⁻ ligands of FeFe hydrogenase

Journal article

The radical S-adenosylmethionine (SAM) enzyme HydG lyses free L-tyrosine to produce CO and CN⁻ for the assembly of the catalytic H cluster of FeFe hydrogenase. We used electron paramagnetic resonance spectroscopy to detect and characterize HydG reaction intermediates generated with a set of ²H, ¹³C, and ¹⁵N nuclear spin-labeled tyrosine substrates. We propose a detailed reaction mechanism in which the radical SAM reaction, initiated at an N-terminal 4Fe-4S cluster, generates a tyrosine radical bound to a C-terminal 4Fe-4S cluster. Heterolytic cleavage of this tyrosine radical at the C_α-C_β bond forms a transient 4-oxidobenzyl (4OB^•) radical and a dehydroglycine bound to the C-terminal 4Fe-4S cluster. Electron and proton transfer to this 4OB^• radical forms p-cresol, with the conversion of this dehydroglycine ligand to Fe-bound CO and CN⁻, a key intermediate in the assembly of the 2Fe subunit of the H cluster.

Authors: Kuchenreuther, J; Myers, W; Stich, T; George, S; NejatyJahromy, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association for the Advancement of Science
• Journal: Science
• Volume: 342
• Issue: 6157
• Pages: 472-475
• Publication date: 2013-10-25
• DOI: 10.1126/science.1241859
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Tyrosine; Catalysis; Catalytic Domain; Carbon Monoxide; S-Adenosylmethionine; Shewanella; Iron-Sulfur Proteins; Hydrogenase; Ligands; Bacterial Proteins