| STRUCTURE |
Scientists comparing a new crystal structure of carbon monoxide dehydrogenase/acetyl-coenzyme A synthase (CODH/ACS) with one published late last year have shown that this enzyme can accommodate a variety of metals in the complex metallocluster it uses to assemble acetyl-CoA [Nat. Struct. Biol., published online March 10, http://dx.doi.org/10.1038/nsb912]. The new structure has stoked the brewing controversy over which of these metals--copper, zinc, or nickel--is used by nature in the catalytically active enzyme. CODH/ACS converts carbon dioxide into acetyl-CoA, a versatile biosynthetic building block. This is accomplished with the help of two different metalloclusters: one in the CODH subunit that reduces CO2 to CO and another in the ACS subunit that assembles acetyl-CoA from CO, a methyl group, and coenzyme A. Late last year, MIT crystallographer Catherine L. Drennan and University of Nebraska biochemist Stephen W. Ragsdale revealed a 2.2-Å X-ray structure of CODH/ACS [Science, 298, 567 (2002)]. Surprisingly, they found that the metal cluster that assembles acetyl-CoA--long thought to consist of just a nickel atom linked to a cube of four iron and four sulfur atoms--also had a copper atom wedged in the middle (C&EN, Oct. 21, 2002, page 13). But crystallographer Juan C. Fontecilla-Camps of the Institute of Structural Biology, Grenoble, France, and biochemist Paul A. Lindahl of Texas A&M University remain unconvinced. The pair have offered a new 1.9-Å structure of CODH/ACS that is reassuringly similar to earlier structure determinations. But, strikingly, the new structure reveals that both Zn and Ni can occupy the Cu site. "The fact that this site can bind at least three different metals' ions brings into question which one the enzyme really uses," Lindahl says. He thinks that the Cu seen in the earlier structure was a fluke resulting from the site's promiscuity. Instead, Lindahl favors Ni in the central spot, pointing to the recent biochemical data supporting an Fe4S4-Ni-Ni site in a related ACS enzyme [J. Biol. Chem., 278, 6101 (2003)]. But Drennan points out that her Cu-containing crystals are capable of converting CO2 to acetyl-CoA. And Ragsdale recently showed that depleting the enzyme of Cu correlates with a drop in activity [Proc. Nat. Acad. Sci. USA, published online Feb. 14, http://www.pnas.org/cgi/content/abstract/0436720100v1]. |
| COMMENTS |
From an inorganic chemist's perspective, "Ni intuitively makes more sense than Cu," says inorganic chemist Charles G. Riordan of the University of Delaware. "But it's still too early to tell whether Cu or Ni provides enzymatic activity." |
| UPDATE | 03.03 |
| AUTHOR |
- Fontecilla-Camps Juan C. (Institut de Biologie Structurale, Frenoble) - Lindahl Paul A. (Texas A&M Uni.) |
| LITERATURE REF. | This data is not available for free |
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