EC 5.6.1.9     
Accepted name: (R)-2-hydroxyacyl-CoA dehydratase activating ATPase
Reaction: 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
Other name(s): archerase; (R)-2-hydroxyacyl-CoA dehydratase activator; (R)-2-hydroxyacyl-CoA dehydratase activase; fldI (gene name); hgdC (gene name); hadI (gene name); lcdC (gene name)
Systematic name: reduced flavodoxin:(R)-2-hydroxyacyl-CoA dehydratase electron transferase (ATP-hydrolyzing)
Comments: 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.
References:
1.  Bendrat, K., Müller, U., Klees, A.G. and Buckel, W. Identification of the gene encoding the activator of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans by gene expression in Escherichia coli. FEBS Lett. 329 (1993) 329–331. [PMID: 8365476]
2.  Müller, U. and Buckel, W. Activation of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. Eur. J. Biochem. 230 (1995) 698–704. [PMID: 7607244]
3.  Locher, K.P., Hans, M., Yeh, A.P., Schmid, B., Buckel, W. and Rees, D.C. Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A. J. Mol. Biol. 307 (2001) 297–308. [PMID: 11243821]
4.  Dickert, S., Pierik, A.J. and Buckel, W. Molecular characterization of phenyllactate dehydratase and its initiator from Clostridium sporogenes. Mol. Microbiol. 44 (2002) 49–60. [PMID: 11967068]
5.  Thamer, W., Cirpus, I., Hans, M., Pierik, A.J., Selmer, T., Bill, E., Linder, D. and Buckel, W. A two [4Fe-4S]-cluster-containing ferredoxin as an alternative electron donor for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. Arch. Microbiol. 179 (2003) 197–204. [PMID: 12610725]
6.  Kim, J., Hetzel, M., Boiangiu, C.D. and Buckel, W. Dehydration of (R)-2-hydroxyacyl-CoA to enoyl-CoA in the fermentation of α-amino acids by anaerobic bacteria. FEMS Microbiol. Rev. 28 (2004) 455–468. [PMID: 15374661]
7.  Kim, J., Darley, D. and Buckel, W. 2-Hydroxyisocaproyl-CoA dehydratase and its activator from Clostridium difficile. FEBS J. 272 (2005) 550–561. [PMID: 15654892]
8.  Kim, J., Darley, D.J., Buckel, W. and Pierik, A.J. An allylic ketyl radical intermediate in clostridial amino-acid fermentation. Nature 452 (2008) 239–242. [PMID: 18337824]
9.  Knauer, S.H., Buckel, W. and Dobbek, H. On the ATP-dependent activation of the radical enzyme (R)-2-hydroxyisocaproyl-CoA dehydratase. Biochemistry 51 (2012) 6609–6622. [PMID: 22827463]
[EC 5.6.1.9 created 2019]