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Updated: Nov 20, 2025

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
Published on: April 26, 2024
Crystallographic Characterization of the Carbonylated A-Cluster in Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase
Steven E Cohen1, Mehmet Can2, Elizabeth C Wittenborn1
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Abstract:
The Wood-Ljungdahl pathway allows for autotrophic bacterial growth on carbon dioxide, with the last step in acetyl-CoA synthesis catalyzed by the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS). ACS uses a complex Ni-Fe-S metallocluster termed the A-cluster to assemble acetyl-CoA from carbon monoxide, a methyl moiety and coenzyme A. Here, we report the crystal structure of CODH/ACS from Moorella thermoacetica with substrate carbon monoxide bound at the A-cluster, a state previously uncharacterized by crystallography. Direct structural characterization of this state highlights the role of second sphere residues and conformational dynamics in acetyl-CoA assembly, the biological equivalent of the Monsanto process.
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