reduced flavodoxin:(R)-2-hydroxyacyl-CoA dehydratase electron transferase (ATP-hydrolyzing)
Reaction(IUBMB)
2 ATP + a reduced flavodoxin + an inactive (R)-2-hydroxyacyl-CoA dehydratase + 2 H2O = 2 ADP + 2 phosphate + a flavodoxin semiquinone + an active (R)-2-hydroxyacyl-CoA dehydratase
Substrate
ATP [CPD:C00002];
reduced flavodoxin [CPD:C02745];
inactive (R)-2-hydroxyacyl-CoA dehydratase;
H2O [CPD:C00001]
Product
ADP [CPD:C00008];
phosphate [CPD:C00009];
flavodoxin semiquinone [CPD:C05199];
active (R)-2-hydroxyacyl-CoA dehydratase
Comment
Members of the (R)-2-hydroxyacyl-CoA dehydratase family (including EC 4.2.1.54, lactoyl-CoA dehydratase, EC 4.2.1.157, (R)-2-hydroxyisocaproyl-CoA dehydratase, EC 4.2.1.167, (R)-2-hydroxyglutaryl-CoA dehydratase and EC 4.2.1.175, (R)-3-(aryl)lactoyl-CoA dehydratase) are two-component systems composed of an activator component and a dehydratase component. The activator is an extremely oxygen-sensitive homodimer with one [4Fe-4S] cluster bound at the dimer interface. Before it can catalyse the dehydration reaction, the dehydratase requires one high-energy electron that is used to transiently reduce the electrophilic thiol ester carbonyl to a nucleophilic ketyl radical anion, facilitating the elimination of the hydroxyl group. The activator, which has been named archerase because its open position resembles an archer shooting arrows, binds two ADP molecules. Upon the reduction of its [4Fe-4S] cluster by a single electron, delivered by a dedicated flavodoxin or a clostridial ferredoxin, the two ADP molecules exchange for two ATP molecules, resulting in a large conformational change. The change allows the activator to bind to the dehydratase component and transfer the electron to it, activating it. During this event the two ATP molecules are hydrolysed and the activator returns to its resting state. Since the electron is regenerated at the end of each reaction cycle of the dehydratase, the activation is required only once, before the first reaction takes place.
Identification of the gene encoding the activator of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans by gene expression in Escherichia coli.
