Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A

Locher, Kaspar P.; Hans, Marcus; Yeh, Andrew; Schmid, Benedikt; Rees, Douglas C.

doi:10.1006/jmbi.2000.4496

Cited by 70 publications

(103 citation statements)

References 39 publications

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“…The CoFeSP activator is also distinct from the Fe protein and the dehydratase activator by its modular architecture (2,13). In these proteins, the electron-donating [4Fe-4S] clusters are not found in an isolated domain like in RACo, but are directly linked to the ATPase site.…”

Section: Discussionmentioning

confidence: 99%

“…The structure of the homodimeric activator of 2-hydroxyglutaryl-CoA dehydratase revealed a [4Fe-4S] cluster covalently linking the two monomers, on a first glance resembling the Fe protein (13). The structure of the activator also showed it to be a member of the ASKHA (acetate and sugar kinases/heat shock protein 70/actin) superfamily.…”

mentioning

confidence: 99%

“…The structure of the activator also showed it to be a member of the ASKHA (acetate and sugar kinases/heat shock protein 70/actin) superfamily. ASKHA proteins catalyze phosphoryl transfers or hydrolysis of ATP in a variety of biological contexts and are distinct from the P loop containing switch-type NTPases to which the Fe protein of nitrogenase belongs (13,14). The binding of two MgATP molecules to the reduced activator is supposed to induce a conformational change and drives formation of the complex with the dehydratase.…”

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confidence: 99%

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Redox-dependent complex formation by an ATP-dependent activator of the corrinoid/iron-sulfur protein

Hennig

Jeoung

Goetzl

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Movement, cell division, protein biosynthesis, electron transfer against an electrochemical gradient, and many more processes depend on energy conversions coupled to the hydrolysis of ATP. The reduction of metal sites with low reduction potentials (E 0 0 < −500 mV) is possible by connecting an energetical uphill electron transfer with the hydrolysis of ATP. The corrinoid-iron/ sulfur protein (CoFeSP) operates within the reductive acetyl-CoA pathway by transferring a methyl group from methyltetrahydrofolate bound to a methyltransferase to the [Ni-Ni-Fe 4 S 4 ] cluster of acetyl-CoA synthase. Methylation of CoFeSP only occurs in the lowpotential Co(I) state, which can be sporadically oxidized to the inactive Co(II) state, making its reductive reactivation necessary. Here we show that an open-reading frame proximal to the structural genes of CoFeSP encodes an ATP-dependent reductive activator of CoFeSP. Our biochemical and structural analysis uncovers a unique type of reductive activator distinct from the electron-transferring ATPases found to reduce the MoFe-nitrogenase and 2-hydroxyacyl-CoA dehydratases. The CoFeSP activator contains an ASKHA domain (acetate and sugar kinases, Hsp70, and actin) harboring the ATP-binding site, which is also present in the activator of 2-hydroxyacyl-CoA dehydratases and a ferredoxin-like [2Fe-2S] cluster domain acting as electron donor. Complex formation between CoFeSP and its activator depends on the oxidation state of CoFeSP, which provides evidence for a unique strategy to achieve unidirectional electron transfer between two redox proteins.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Redox-dependent complex formation by an ATP-dependent activator of the corrinoid/iron-sulfur protein

Hennig

Jeoung

Goetzl

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…RACo is homologous to other reductive activators of corrinoid enzymes 6 , which are members of the ASKHA-ATPase family 7 . Nitrogenase reductase, also called Fe protein 8 , the activator of atypical dehydratases 9 and reductive activators of corrinoid enzymes proteins are the three principal types of ATPases coupling ATP hydrolysis to an energetically uphill electron transfer. All three proteins consist of an ATPase module and a Fe/S-cluster module linked to the ATPase site.…”

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confidence: 99%

ATP-induced electron transfer by redox-selective partner recognition

et al. 2014

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Thermodynamically unfavourable electron transfers are enabled by coupling to an energysupplying reaction. How the energy is transduced from the exergonic to the endergonic process is largely unknown. Here we provide the structural basis for an energy transduction process in the reductive activation of B 12 -dependent methyltransferases. The transfer of one electron from an activating enzyme to the cobalamin cofactor is energetically uphill and relies on coupling to an ATPase reaction. Our results demonstrate that the key to coupling is, besides the oxidation state-dependent complex formation, the conformational gating of the electron transfer. Complex formation induces a substitution of the ligand at the electronaccepting Co ion. Addition of ATP initiates electron transfer by provoking conformational changes that destabilize the complex. We show how remodelling of the electron-accepting Co 2 þ promotes ATP-dependent electron transfer; an efficient strategy not seen in other electron-transferring ATPases.

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“…The monodimeric activase of this enzyme system catalyzes a nonstoichiometric ATPdependent activation of electrons that are essential for the initiation of water elimination from the ␣-position of 2-hydroxyglutaryl-CoA (7,14). Based on conserved amino acid motifs (11,13) and on the recently solved structure of activase from A. fermentans (15), BCR is postulated to contain two functionally distinct modules ( Fig. 2): (i) Bcr A and Bcr D (␣-and ␦-subunits) both contain one ATP-binding site.…”

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confidence: 99%

Mechanism of ATP-driven electron transfer catalyzed by the benzene ring-reducing enzyme benzoyl- CoA reductase

Unciuleac

Boll

2001

Proc. Natl. Acad. Sci. U.S.A.

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Benzoyl-CoA reductase (BCR) from the bacterium Thauera aromatica catalyzes the two-electron reduction of benzoyl-CoA (BCoA) to a nonaromatic cyclic diene. In a process analogous to enzymatic nitrogen reduction, BCR couples the electron transfer to the aromatic ring to a stoichiometric hydrolysis of 2 ATP͞2e ؊ . Reduced but not oxidized BCR hydrolyzes ATP to ADP. In this work, purified BCR was shown to catalyze an isotope exchange from [ 14 C]ADP to [ 14 C]ATP, which was Ϸ15% of the ATPase activity in the presence of equimolar amounts of ADP and ATP. In accordance, BCR (␣␤␥␦-composition) autophosphorylated its ␥-subunit when incubated with [␥-32 P]ATP. Formation of the enzyme-phosphate was independent of the redox state, whereas only dithionitereduced BCR catalyzed a dephosphorylation associated with the ATPase activity. This finding suggests that the ATPase-and autophosphatase-partial activities of BCR exhibit identical redox dependencies. BCoA or the nonphysiological electron-accepting substrate hydroxylamine stimulated the redox-dependent effects; the rates of both the overall ATPase and the autophosphatase activities of reduced BCR were increased 6-fold. In contrast, BCoA and hydroxylamine had no effect on oxidized and phosphorylated BCR. The reactivity of the phosphoamino acid fits best with a phosphoamidate or acylphosphate linkage. The results obtained suggest a mechanism of ATP hydrolysis-driven electron transfer, which differs from that of nitrogenase by the transient formation of a phosphorylated enzyme.B enzoyl-CoA (BCoA) is a central intermediate in the metabolism of many aromatic compounds in anaerobic bacteria. This compound becomes reduced by benzoyl-CoA reductase (BCR), a key enzyme in anaerobic aromatic metabolism (1, 2). It catalyzes the reductive dearomatization of BCoA to cyclohexa-1,5-diene-1-carbonyl-CoA ( Fig. 1; ref. 3). In this reaction, the hydrolysis of two ATP to ADP and Pi is stoichiometrically coupled to the transfer of two single electrons from reduced ferredoxin to the aromatic substrate. Notably, BCR also catalyzes the ATP-dependent reduction of the nonphysiological substrate hydroxylamine (2). The stoichiometric coupling of ATP hydrolysis to an electron transfer process has long been considered as a unique feature of nitrogenases (4, 5). However, there are no amino acid sequence similarities between BCR and nitrogenases.The reduction of the aromatic ring is a mechanistically and energetically difficult process that in organic synthesis requires solvated electrons, which are generated by dissolving alkali metals in liquid ammonia. In a so-called Birch mechanism, the reduction of the aromatic ring proceeds in single electron and proton transfer steps by means of radical intermediates (6). A similar mechanism has been proposed for enzymatic benzene ring reduction (7). The crucial step is the first electron transfer to the aromatic ring yielding a nonaromatic radical anion, which requires a redox potential of Ϫ1.9 V (3). BCR overcomes this high redox barrier by coupling a stoichiomet...

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Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A

Cited by 70 publications

References 39 publications

Redox-dependent complex formation by an ATP-dependent activator of the corrinoid/iron-sulfur protein

Redox-dependent complex formation by an ATP-dependent activator of the corrinoid/iron-sulfur protein

ATP-induced electron transfer by redox-selective partner recognition

Mechanism of ATP-driven electron transfer catalyzed by the benzene ring-reducing enzyme benzoyl- CoA reductase

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