Functional copper at the acetyl-CoA synthase active site

Javier Seravalli, Weiwei Gu, Annie Tam, Erick Strauss, Tadhg P. Begley, Stephen P. Cramer, Stephen W. Ragsdale

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


The bifunctional CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) plays a central role in the Wood-Ljungdahl pathway of autotrophic CO2 fixation. A recent structure of the Moorella thermoacetica enzyme revealed that the ACS active site contains a [4Fe-4S] cluster bridged to a binuclear Cu-Ni site. Here, biochemical and x-ray absorption spectroscopic (XAS) evidence is presented that the copper ion at the M. thermoacetica ACS active site is essential. Depletion of copper correlates with reduction in ACS activity and in intensity of the "NiFeC" EPR signal without affecting either the activity or the EPR spectroscopic properties associated with CODH. In contrast, Zn content is negatively correlated with ACS activity without any apparent relationship to CODH activity. Cu is also found in the methanogenic CODH/ACS from Methanosarcina thermophila. XAS studies are consistent with a distorted Cu(I)-S3 site in the fully active enzyme in solution. Cu extended x-ray absorption fine structure analysis indicates an average Cu-S bond length of 2.25 Å and a metal neighbor at 2.65 Å, consistent with the Cu-Ni distance observed in the crystal structure. XAS experiments in the presence of seleno-CoA reveal a Cu-S3Se environment with a 2.4-Å Se-Cu bond, strongly implicating a Cu-SCoA intermediate in the mechanism of acetyl-CoA synthesis. These results indicate an essential and functional role for copper in the CODH/ACS from acetogenic and methanogenic organisms.

Original languageEnglish (US)
Pages (from-to)3689-3694
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Functional copper at the acetyl-CoA synthase active site'. Together they form a unique fingerprint.

Cite this