Cysteine as a ligand platform in the biosynthesis of the FeFe hydrogenase H cluster
- Department of Chemistry, University of California, Davis, CA 95616,
- Department of Chemical Engineering, Stanford University, Stanford, CA 94305,
- Department of Chemical Engineering, Stanford University, Stanford, CA 94305,, Department of Bioengineering, Stanford University, Stanford, CA 94305
Hydrogenases catalyze the redox interconversion of protons and H2, an important reaction for a number of metabolic processes and for solar fuel production. In FeFe hydrogenases, catalysis occurs at the H cluster, a metallocofactor comprising a [4Fe–4S]H subcluster coupled to a [2Fe]H subcluster bound by CO, CN–, and azadithiolate ligands. The [2Fe]H subcluster is assembled by the maturases HydE, HydF, and HydG. HydG is a member of the radical S-adenosyl-L-methionine family of enzymes that transforms Fe and L-tyrosine into an [Fe(CO)2(CN)] synthon that is incorporated into the H cluster. Though it is thought that the site of synthon formation in HydG is the “dangler” Fe of a [5Fe] cluster, many mechanistic aspects of this chemistry remain unresolved including the full ligand set of the synthon, how the dangler Fe initially binds to HydG, and how the synthon is released at the end of the reaction. In order to address these questions, we show in this paper that L-cysteine (Cys) binds the auxiliary [4Fe–4S] cluster of HydG and further chelates the dangler Fe. We demonstrate that a [4Fe–4S]aux[CN] species is generated during HydG catalysis, a process that entails the loss of Cys and the [Fe(CO)2(CN)] fragment; on this basis, we suggest that Cys likely completes the coordination sphere of the synthon. Finally, through spectroscopic analysis of HydG before and after the synthon is formed, we conclude that Cys serves as the ligand platform on which the synthon is built and plays a role in both Fe2+ binding and synthon release.
- Research Organization:
- Stanford Univ., CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
- Grant/Contract Number:
- FG02-09ER46632; SC0002010; GM111025; GM104543; GM65440
- OSTI ID:
- 1235132
- Alternate ID(s):
- OSTI ID: 1356198
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 112 Journal Issue: 37; ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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