Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica

Troy A. Stich, Javier Seravalli, Swarnalatha Venkateshrao, Thomas G. Spiro, Stephen W. Ragsdale, Thomas C. Brunold

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Methyl transfer reactions are important in a number of biochemical pathways. An important class of methyltransferases uses the cobalt cofactor cobalamin, which receives a methyl group from an appropriate methyl donor protein to form an intermediate organometallic methyl-Co bond that subsequently is cleaved by a methyl acceptor. Control of the axial ligation state of cobalamin influences both the mode (i.e., homolytic vs heterolytic) and the rate of Co-C bond cleavage. Here we have studied the axial ligation of a corrinoid iron-sulfur protein (CFeSP) that plays a key role in energy generation and cell carbon synthesis by anaerobic microbes, such as methanogenic archaea and acetogenic bacteria. This protein accepts a methyl group from methyltetrahydrofolate forming Me-Co3+CFeSP that then donates a methyl cation (Me) from Me-Co3+CFeSP to a nickel site on acetyl-CoA synthase. To unambiguously establish the binding scheme of the corrinoid cofactor in the CFeSP, we have combined resonance Raman, magnetic circular dichroism, and EPR spectroscopic methods with computational chemistry. Our results clearly demonstrate that the Me-Co3+ and Co2+ states of the CFeSP have an axial water ligand like the free MeCbi+ and Co2+Cbi+ cofactors; however, the Co-OH2 bond length is lengthened by about 0.2 Å for the protein-bound cofactor. Elongation of the Co-OH2 bond of the CFeSP-bound cofactor is proposed to make the cobalt center more "Co1--like", a requirement to facilitate heterolytic Co-C bond cleavage.

Original languageEnglish (US)
Pages (from-to)5010-5020
Number of pages11
JournalJournal of the American Chemical Society
Volume128
Issue number15
DOIs
StatePublished - Apr 19 2006

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Corrinoids
Sulfur
Vitamin B 12
Iron
Cobalt
Proteins
Ligation
Iron-Sulfur Proteins
Computational chemistry
Acetyl Coenzyme A
Archaea
Methyltransferases
Bond length
Organometallics
Circular Dichroism
Nickel
Paramagnetic resonance
Cations
Elongation
Bacteria

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica. / Stich, Troy A.; Seravalli, Javier; Venkateshrao, Swarnalatha; Spiro, Thomas G.; Ragsdale, Stephen W.; Brunold, Thomas C.

In: Journal of the American Chemical Society, Vol. 128, No. 15, 19.04.2006, p. 5010-5020.

Research output: Contribution to journalArticle

Stich, Troy A. ; Seravalli, Javier ; Venkateshrao, Swarnalatha ; Spiro, Thomas G. ; Ragsdale, Stephen W. ; Brunold, Thomas C. / Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica. In: Journal of the American Chemical Society. 2006 ; Vol. 128, No. 15. pp. 5010-5020.
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