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Heme Concentration Dependence and Metalloporphyrin Inhibition of the System I and II Cytochrome c Assembly Pathways ^,

Cynthia L. Richard-Fogal, Elaine R. Frawley, Robert E. Feissner, and Robert G. Kranz^*

Department of Biology, Campus Box 1137, Washington University, 1 Brookings Drive, St. Louis, Missouri 63130¹

Received 30 August 2006/ Accepted 21 October 2006

Studies have indicated that specific heme delivery to apocytochrome c is a critical feature of the cytochrome c biogenesis pathways called system I and II. To determine directly the heme requirements of each system, including whether other metal porphyrins can be incorporated into cytochromes c, we engineered Escherichia coli so that the natural system I (ccmABCDEFGH) was deleted and exogenous porphyrins were the sole source of porphyrins (hemA). The engineered E. coli strains that produced recombinant system I (from E. coli) or system II (from Helicobacter) facilitated studies of the heme concentration dependence of each system. Using this exogenous porphyrin approach, it was shown that in system I the levels of heme used are at least fivefold lower than the levels used in system II, providing an important advantage for system I. Neither system could assemble holocytochromes c with other metal porphyrins, suggesting that the attachment mechanism is specific for Fe protoporphyrin. Surprisingly, Zn and Sn protoporphyrins are potent inhibitors of the pathways, and exogenous heme competes with this inhibition. We propose that the targets are the heme binding proteins in the pathways (CcmC, CcmE, and CcmF for system I and CcsA for system II).

Published ahead of print on 3 November 2006.

Supplemental material for this article may be found at http://jb.asm.org/.

Present address: Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642.

This article has been cited by other articles:

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