Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.12.7.2 (hydrogenase)
 3,522 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogenases have clear evolutionary links to the much more complex NADH-ubiquinone oxidoreductases (Complex I). Certain membrane-bound [NiFe]-hydrogenases presumably pump protons. From a detailed comparison of hydrogenases and Complex I, it is concluded here that the TYKY subunit in these enzymes is a special 2[4Fe-4S] ferredoxin, which functions as the electrical driving unit for a proton pump. The comparison further revealed that the flavodoxin fold from [NiFe]-hydrogenases is presumably conserved in the PSST subunit of Complex I. It is proposed that bovine Complex I and the soluble NAD(+)-reducing hydrogenase from Ralstonia eutropha each contain a second FMN group.
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PMID:Learning from hydrogenases: location of a proton pump and of a second FMN in bovine NADH--ubiquinone oxidoreductase (Complex I). 1108 55

From phylogenetic sequence analysis, it can be concluded that the proton-pumping NADH:ubiquinone oxidoreductase (complex I) has evolved from preexisting modules for electron transfer and proton translocation. It is built up by a peripheral NADH dehydrogenase module, an amphipatic hydrogenase module, and a membrane-bound transporter module. These modules, or at least part of them, are also present in various other bacterial enzymes. It is assumed that they fulfill a similar function in complex I and related enzymes. Based on the function of the individual modules, it is possible to speculate about the mechanism of complex I. The hydrogenase module might work as a redox-driven proton pump, while the transporter module might act as a conformation-driven proton pump. This implies that complex I contains two energy-coupling sites. The NADH dehydrogenase module seems to be involved in electron transfer and not in proton translocation.
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PMID:Complex I: a chimaera of a redox and conformation-driven proton pump? 1169 26

Methanosarcina mazei belongs to the group of aceticlastic methanogens and converts acetate into the potent greenhouse gases CO(2) and CH(4). The aceticlastic respiratory chain involved in methane formation comprises the three transmembrane proteins Ech hydrogenase, F(420) nonreducing hydrogenase and heterodisulfide reductase. It has been shown that the latter two contribute to the proton motive force. The data presented here clearly demonstrate that Ech hydrogenase is also involved in energy conservation. ATP synthesis was observed in a cytoplasm-free vesicular system of Ms. mazei that was dependent on the oxidation of reduced ferredoxin and the formation of molecular hydrogen (as catalysed by Ech hydrogenase). Such an ATP formation was not observed in a Deltaech mutant strain. The protonophore 3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (SF6847) led to complete inhibition of ATP formation in the Ms. mazei wild-type without inhibiting hydrogen production by Ech hydrogenase, whereas the sodium ion ionophore ETH157 did not affect ATP formation in this system. Thus, we conclude that Ech hydrogenase acts as primary proton pump in a ferredoxin-dependent electron transport system.
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PMID:Involvement of Ech hydrogenase in energy conservation of Methanosarcina mazei. 2062 48

Organohalide respiring bacteria (ORB) are capable of utilising organohalides as electron acceptors for the generation of cellular energy and consequently play an important role in the turnover of natural and anthropogenically-derived organohalides. In this study, the response of a Dehalobacter sp. strain UNSWDHB to the addition of trichloromethane (TCM) after a 50 h period of its absence (suffocation) was evaluated from a transcriptomic and proteomic perspective. The up-regulation of TCM reductive dehalogenase genes (tmrABC) and their gene products (TmrABC) was confirmed at both transcriptional and proteomic levels. Other findings include the upregulation of various hydrogenases (membrane-associated Ni-Fe hydrogenase complexes and soluble Fe-Fe hydrogenases), formate dehydrogenases, complex I and a pyrophosphate-energized proton pump. The elevated expression of enzymes associated with carbon metabolism, including complete Wood Ljungdahl pathway, during TCM respiration raises interesting questions on possible fates of intracellular formate and its potential role in the physiology of this bacterium. Overall, the findings presented here provide a broader view on the bioenergetics and general physiology of Dehalobacter UNSWDHB cells actively respiring with TCM.
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PMID:Genomic, transcriptomic and proteomic analyses of Dehalobacter UNSWDHB in response to chloroform. 2745

Numerous recent developments in the biochemistry, molecular biology, and physiology of formate and H2 metabolism and of the [NiFe]-hydrogenase (Hyd) cofactor biosynthetic machinery are highlighted. Formate export and import by the aquaporin-like pentameric formate channel FocA is governed by interaction with pyruvate formate-lyase, the enzyme that generates formate. Formate is disproportionated by the reversible formate hydrogenlyase (FHL) complex, which has been isolated, allowing biochemical dissection of evolutionary parallels with complex I of the respiratory chain. A recently identified sulfido-ligand attached to Mo in the active site of formate dehydrogenases led to the proposal of a modified catalytic mechanism. Structural analysis of the homologous, H2-oxidizing Hyd-1 and Hyd-5 identified a novel proximal [4Fe-3S] cluster in the small subunit involved in conferring oxygen tolerance to the enzymes. Synthesis of Salmonella Typhimurium Hyd-5 occurs aerobically, which is novel for an enterobacterial Hyd. The O2-sensitive Hyd-2 enzyme has been shown to be reversible: it presumably acts as a conformational proton pump in the H2-oxidizing mode and is capable of coupling reverse electron transport to drive H2 release. The structural characterization of all the Hyp maturation proteins has given new impulse to studies on the biosynthesis of the Fe(CN)2CO moiety of the [NiFe] cofactor. It is synthesized on a Hyp-scaffold complex, mainly comprising HypC and HypD, before insertion into the apo-large subunit. Finally, clear evidence now exists indicating that Escherichia coli can mature Hyd enzymes differentially, depending on metal ion availability and the prevailing metabolic state. Notably, Hyd-3 of the FHL complex takes precedence over the H2-oxidizing enzymes.
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PMID:Anaerobic Formate and Hydrogen Metabolism. 2773 84

Under anaerobic conditions, Escherichia coli is able to metabolize molecular hydrogen via the action of several [NiFe]-hydrogenase enzymes. Hydrogenase-2, which is typically present in cells at low levels during anaerobic respiration, is a periplasmic-facing membrane-bound complex that functions as a proton pump to convert energy from hydrogen (H2) oxidation into a proton gradient; consequently, its structure is of great interest. Empirically, the complex consists of a tightly bound core catalytic module, comprising large (HybC) and small (HybO) subunits, which is attached to an Fe-S protein (HybA) and an integral membrane protein (HybB). To date, efforts to gain a more detailed picture have been thwarted by low native expression levels of Hydrogenase-2 and the labile interaction between HybOC and HybA/HybB subunits. In the present paper, we describe a new overexpression system that has facilitated the determination of high-resolution crystal structures of HybOC and, hence, a prediction of the quaternary structure of the HybOCAB complex.
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PMID:The structure of hydrogenase-2 from Escherichia coli: implications for H2-driven proton pumping. 2955 44

Microbial electrosynthesis is an emerging technology with the potential to simultaneously store renewably generated energy, fix carbon dioxide, and produce high-value organic compounds. However, limited understanding of the route of electrons into the cell remains an obstacle to developing a robust microbial electrosynthesis platform. To address this challenge, we leveraged the native extracellular electron transfer pathway in Shewanella oneidensis MR-1 to connect an extracellular electrode with an intracellular reduction reaction. The system uses native Mtr proteins to transfer electrons from an electrode to the inner membrane quinone pool. Subsequently, electrons are transferred from quinones to NAD+ by native NADH dehydrogenases. This reverse functioning of NADH dehydrogenases is thermodynamically unfavorable; therefore, we added a light-driven proton pump (proteorhodopsin) to generate proton-motive force to drive this activity. Finally, we use reduction of acetoin to 2,3-butanediol via a heterologous butanediol dehydrogenase (Bdh) as an electron sink. Bdh is an NADH-dependent enzyme; therefore, observation of acetoin reduction supports our hypothesis that cathodic electrons are transferred to intracellular NAD+. Multiple lines of evidence indicate proper functioning of the engineered electrosynthesis system: electron flux from the cathode is influenced by both light and acetoin availability, and 2,3-butanediol production is highest when both light and a poised electrode are present. Using a hydrogenase-deficient S. oneidensis background strain resulted in a stronger correlation between electron transfer and 2,3-butanediol production, suggesting that hydrogen production is an off-target electron sink in the wild-type background. This system represents a promising step toward a genetically engineered microbial electrosynthesis platform and will enable a new focus on synthesis of specific compounds using electrical energy.
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PMID:Reversing an Extracellular Electron Transfer Pathway for Electrode-Driven Acetoin Reduction. 3124 80

Complex I is the largest and most intricate redox-driven proton pump of the respiratory chain. The structure of bacterial and mitochondrial complex I has been determined by X-ray crystallography and cryo-EM at increasing resolution. The recent cryo-EM structures of the complex I-like NDH complex and membrane bound hydrogenase open a new and more comprehensive perspective on the complex I superfamily. Functional studies and molecular modeling approaches have greatly advanced our understanding of the catalytic cycle of complex I. However, the molecular mechanism by which energy is extracted from the redox reaction and utilized to drive proton translocation is unresolved and a matter of ongoing debate. Here, we review progress in structure determination and functional characterization of complex I and discuss current mechanistic models.
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PMID:Respiratory complex I - Mechanistic insights and advances in structure determination. 3193 61