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IUBMB CommentsMembers 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.
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reduced flavodoxin:(R)-2-hydroxyacyl-CoA dehydratase electron transferase (ATP-hydrolyzing)
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.
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2 ATP + a reduced ferredoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + an oxidized ferredoxin + active 2-hydroxyglutaryl-CoA dehydratase
2 ATP + a reduced flavodoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyglutaryl-CoA dehydratase
2 ATP + a reduced flavodoxin + inactive 2-hydroxyisocaproyl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyisocaproyl-CoA dehydratase
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2 ATP + a reduced flavodoxin + inactive phenyllactate dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active phenyllactate dehydratase
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additional information
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2 ATP + a reduced ferredoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + an oxidized ferredoxin + active 2-hydroxyglutaryl-CoA dehydratase
a two [4Fe-4S]-cluster-containing ferredoxin with redox potentials of -405 mV and -340 mV can serve as an alternative electron donor
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2 ATP + a reduced ferredoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + an oxidized ferredoxin + active 2-hydroxyglutaryl-CoA dehydratase
a two [4Fe-4S]-cluster-containing ferredoxin with redox potentials of -405 mV and -340 mV can serve as an alternative electron donor
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2 ATP + a reduced flavodoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyglutaryl-CoA dehydratase
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2 ATP + a reduced flavodoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyglutaryl-CoA dehydratase
only catalytic amounts of activator HgdC are required for complete activation of the dehydratase
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2 ATP + a reduced flavodoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyglutaryl-CoA dehydratase
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2 ATP + a reduced flavodoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyglutaryl-CoA dehydratase
only catalytic amounts of activator HgdC are required for complete activation of the dehydratase
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2 ATP + a reduced flavodoxin + inactive 2-hydroxyglutaryl-CoA dehydratase + 2 H2O
2 ADP + 2 phosphate + a flavodoxin semiquinone + active 2-hydroxyglutaryl-CoA dehydratase
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additional information
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the activation of the dehydratase requires only ATP
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additional information
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oxidized component A exhibits ATPase activity of 6 s-1, which is completely abolished upon reduction by one electron. In the presence of ATP, one electron is transferred from flavodoxin hydroquinone via the [4Fe-4S]1+/2+ cluster of component A to Mo(VI) of 2-hydroxyglutaryl-CoA dehydratase, which is thereby reduced to Mo(V)
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additional information
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the hydroquinone state of a flavodoxin serves as one-electron donor of component A, whereby the blue semiquinone is formed. Flavodoxin is the dominant electron donor protein under iron-limiting conditions
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additional information
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the hydroquinone state of a flavodoxin serves as one-electron donor of component A, whereby the blue semiquinone is formed. Flavodoxin is the dominant electron donor protein under iron-limiting conditions
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additional information
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oxidized component A exhibits ATPase activity of 6 s-1, which is completely abolished upon reduction by one electron. In the presence of ATP, one electron is transferred from flavodoxin hydroquinone via the [4Fe-4S]1+/2+ cluster of component A to Mo(VI) of 2-hydroxyglutaryl-CoA dehydratase, which is thereby reduced to Mo(V)
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additional information
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the activation of the dehydratase requires only ATP
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Thamer, W.; Cirpus, I.; Hans, M.; Pierik, A.; Selmer, T.; Bill, E.; Linder, D.; 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
197-204
2003
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Hans, M.; Bill, E.; Cirpus, I.; Pierik, A.; Hetzel, M.; Alber, D.; Buckel, W.
Adenosine triphosphate-induced electron transfer in 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans
Biochemistry
41
5873-5882
2002
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Knauer, S.; Buckel, W.; Dobbek, H.
On the ATP-dependent activation of the radical enzyme (R)-2-hydroxyisocaproyl-CoA dehydratase
Biochemistry
51
6609-6622
2012
Clostridioides difficile (Q5U925)
brenda
Kim, J.; Pierik, A.; Buckel, W.
A complex of 2-Hydroxyisocaproyl-Coenzyme A dehydratase and its activator from clostridium difficile stabilized by aluminium tetrafluoride-adenosine diphosphate
Chemphyschem
11
1307-1312
2010
Clostridioides difficile (Q5U925)
brenda
Schweiger, G.; Dutscho, R.; Buckel, W.
Purification of 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. An iron-sulfur protein
Eur. J. Biochem.
169
441-448
1987
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Mueller, U.; Buckel, W.
Activation of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans
Eur. J. Biochem.
230
698-704
1995
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Hans, M.; Sievers, J.; Mueller, U.; Bill, E.; Vorholt, J.; Linder, D.; Buckel, W.
2-hydroxyglutaryl-CoA dehydratase from Clostridium symbiosum
Eur. J. Biochem.
265
404-414
1999
[Clostridium] symbiosum (Q9X5B6)
brenda
Kim, J.; Darley, D.; Buckel, W.
2-Hydroxyisocaproyl-CoA dehydratase and its activator from Clostridium difficile
FEBS J.
272
550-561
2005
Clostridioides difficile (Q5U925)
brenda
Bendrat, K.; Mueller, U.; Klees, A.; 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
329-331
1993
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Hans, M.; Buckel, W.; Bill, E.
Spectroscopic evidence for an all-ferrous [4Fe-4S]0 cluster in the superreduced activator of 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans
J. Biol. Inorg. Chem.
13
563-574
2008
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Locher, K.; Hans, M.; Yeh, A.; Schmid, B.; Buckel, W.; Rees, D.
Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A
J. Mol. Biol.
307
297-308
2001
Acidaminococcus fermentans (P11568), Acidaminococcus fermentans, Acidaminococcus fermentans DSM 20731 (P11568)
brenda
Dickert, S.; Pierik, A.J.; Buckel, W.
Molecular characterization of phenyllactate dehydratase and its initiator from Clostridium sporogenes
Mol. Microbiol.
44
49-60
2002
Clostridium sporogenes (Q93AM0)
brenda
5.6.1.9 (R)-2-hydroxyacyl-CoA dehydratase activating ATPase
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