Desaturases fused to their electron donor

Abstract

Fatty acid desaturations in the carboxy-terminal segment from C1—C10 are catalyzed in many, but not in all cases, by desaturase enzymes which are fused to their electron donor cytochrome b5. Several of these enzymes (“front-end desaturases”) from a wide variety of organisms have been cloned and functionally expressed for proof of regio-, stereo- and chain length-selectivity. In most cases the actual status of the substrate chain, whether coenzyme A thioester or component of a membrane lipid, is not known. The cytochrome b5 domain is located N-terminally, internally or C-terminally. Compared to the free cytochrome b5 , the fused domains show a significant reduction of acidic amino acid residues on the surface of the four helices enclosing the heme group. It is discussed how this may contribute to hydrophobic domain pairing required for interdomain electron transport. This is in contrast to the mode of interaction of free cytochrome b5 with its partners, which is governed by electrostatic charge pairing. A look at crystallized or computer-simulated models involving fused or free cytochrome b5 helps to outline the problems encountered by optimizing the docking of partners and the exchange of electrons between domains of different degrees of mobility.