Cytochromes P460 and c′-β: exploiting a novel fold for multiple functions

Abstract

Two related classes of ligand-binding heme c -containing proteins with a high degree of structural homology have been identified and characterized over recent decades: cytochromes P460 (cyts P460), defined by an unusual heme-lysine cross-link, and cytochromes c ′-β (cyts c ′-β), containing a canonical c -heme without the lysine cross-link. The shared protein fold of the cyt P460-cyt c ′-β superfamily can accommodate a variety of heme environments with entirely different reactivities. On the one hand, cyts P460 with polar distal pockets have been shown to oxidize NH 2 OH to NO and/or N 2 O via proton-coupled electron transfer. On the other hand, cyts c ′-β with hydrophobic distal pockets have a proposed gas binding function similar to the unrelated, but more extensively characterized, alpha helical cytochromes c ′. Recent studies have also identified ‘halfway house’ proteins (cyts P460 with non-polar heme pockets and cyts c ′-β with polar distal heme pockets) with functions yet to be resolved. Here, we review the structural, spectroscopic and enzymatic properties of the cyt P460-cyt c ′-β superfamily with a view to understanding the structural determinants of their different functional properties. Graphical abstract

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