Tripping the light fantastic in membrane redox biology: Linking dynamic structures to function in ER electron transfer chains

How the dynamics of proteins assist catalysis is a contemporary issue in
enzymology. In particular, this holds true for membrane-bound enzymes, where
multiple structural, spectroscopic, and biochemical approaches are needed to
build up a comprehensive picture of how dynamics influence enzyme reaction
cycles. Of note are the recent studies of cytochrome P450 reductases (CPR)–P450
(CYP) endoplasmic reticulum (ER) redox chains, showing the relationship
between dynamics and electron flow through flavin and haem redox centres and
the impact this has on monooxygenation chemistry. These studies have led to
deeper understanding of mechanisms of electron flow, including the timing and
control of electron delivery to protein-bound cofactors needed to facilitate CYPcatalysed reactions. Individual and multiple component systems have been used to capture biochemical behaviour and these have led to the emergence of more integrated models of catalysis. Crucially, the effects of membrane environment and composition on reaction cycle chemistry have also been probed, including effects on coenzyme binding/release, thermodynamic control of electron transfer, conformational coupling between partner proteins and vectorial versus ‘off pathway’ electron flow. Here, we review these studies and discuss evidence for the emergence of dynamic structural models of electron flow along human microsomal CPR–P450 redox chains.