Mechanisms and Control of Heme Transport and Incorporation into Cytochrome c.

Abstract

Cytochrome c (cyt c) is ubiquitous in nature, having evolved billions of years ago to function in respiration and photosynthesis. All c-type cytochromes require covalently attached heme, typically at a CXXCH motif. We highlight new studies from the past five years that address the structural and mechanistic bases for the three cyt c biogenesis pathways (Systems I-III). The solved structures of most of the proteins that comprise these systems provide insights into heme transport, the binding of heme, and the mechanism of apocytochrome c (apocyt c) interaction with the synthases. Detailed analyses of the active sites of each cyt c synthase have elucidated chemical mechanisms underlying cyt c biogenesis and their potential as novel antimicrobial targets. This potential is suggested from an evolutionary perspective, as bacteria use two pathways (Systems I and II) that are structurally and mechanistically distinct from the mitochondrial System III. Genomic analyses of bacteria's respiratory capacity, including their use of c-type cytochromes, reveal how the inhibition of cyt c biogenesis could attenuate growth.