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A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase
Tzanko I. Doukov,1Tina M. Iverson,1*Javier Seravalli,2Stephen W. Ragsdale,2Catherine L. Drennan1
A metallocofactor containing iron, sulfur, copper, and nickel has
been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA(coenzyme A) synthase from Moorella thermoacetica (f.
Clostridiumthermoaceticum). Our structure at 2.2 angstrom
resolution revealsthat the cofactor responsible for the assembly of
acetyl-CoA containsa [Fe4S4] cubane bridged
to a copper-nickel binuclear site. Thepresence of these three metals
together in one cluster was unanticipatedand suggests a newly
discovered role for copper in biology. Thedifferent active sites of
this bifunctional enzyme complex areconnected via a channel, 138 angstroms long, that provides a conduitfor carbon monoxide generated
at the C-cluster on one subunitto be incorporated into acetyl-CoA at
the A-cluster on the othersubunit.
1 Department of Chemistry, Massachusetts
Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Biochemistry, Beadle Center,
University of Nebraska, Lincoln, NE 68588, USA.
*
Present address: Division of Biomedical Sciences, MPC, Imperial
College of Science, Technology and Medicine, London SW7 2AZ,UK.
To whom correspondence should be addressed. E-mail:
cdrennan{at}mit.edu
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