Identification of a Bis-molybdopterin Intermediate in Molybdenum Cofactor Biosynthesis in Escherichia coli

Reschke, Stefan; Sigfridsson, Kajsa G.V.; Kaufmann, Paul; Leidel, Nils; Horn, Sebastian; Gast, Klaus; Schulzke, Carola; Haumann, Michael; Leimkühler, Silke

doi:10.1074/jbc.m113.497453

Cited by 45 publications

(78 citation statements)

References 48 publications

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“…Metal analysis by ICP-MS was performed as a service by the School of Chemistry, University of Edinburgh. TXRF analysis was carried out on a PicoFox spectrometer (Bruker) as previously described (49,50). A gallium elemental concentration standard (Sigma) was added to the protein solutions (1:1 vol/vol) before the measurements.…”

Section: Methodsmentioning

confidence: 99%

Bacterial formate hydrogenlyase complex

McDowall

Murphy

Haumann

et al. 2014

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

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Significance The isolation of an active formate hydrogenlyase is a breakthrough in understanding the molecular basis of bacterial hydrogen production. For over 100 years, Escherichia coli has been known to evolve H 2 when cultured under fermentative conditions. Glucose is metabolized to formate, which is then oxidized to CO 2 with the concomitant reduction of protons to H 2 by a single complex called formate hydrogenlyase, which had been genetically, but never biochemically, characterized. In this study, innovative molecular biology and electrochemical experiments reveal a hydrogenase enzyme with the unique ability to sustain H 2 production even under high partial pressures of H 2 . Harnessing bacterial H 2 production offers the prospect of a source of fully renewable H 2 energy, freed from any dependence on fossil fuel.

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Section: Methodsmentioning

confidence: 99%

Bacterial formate hydrogenlyase complex

McDowall

Murphy

Haumann

et al. 2014

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

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219

238

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“…tuberculosis also possesses a homolog of mobA (Rv2453c), which has been implicated in the production of bis-MGD in E. coli through the formation of a bis-MoCo intermediate and subsequent addition of two guanine residues on the terminal phosphate groups (15,19). Of the eight molybdoenzymes identified through bioinformatic analysis of the M. tuberculosis proteome, four are predicted to utilize bis-MGD: Rv0197, Rv1161 (NarG), Rv1442 (BisC), and Rv2900c (FdhF) (2) ( Table 1).…”

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confidence: 99%

bis -Molybdopterin Guanine Dinucleotide Is Required for Persistence of Mycobacterium tuberculosis in Guinea Pigs

et al. 2015

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e Mycobacterium tuberculosis is able to synthesize molybdopterin cofactor (MoCo), which is utilized by numerous enzymes that catalyze redox reactions in carbon, nitrogen, and sulfur metabolism. In bacteria, MoCo is further modified through the activity of a guanylyltransferase, MobA, which converts MoCo to bis-molybdopterin guanine dinucleotide (bis-MGD), a form of the cofactor that is required by the dimethylsulfoxide (DMSO) reductase family of enzymes, which includes the nitrate reductase NarGHI. In this study, the functionality of the mobA homolog in M. tuberculosis was confirmed by demonstrating the loss of assimilatory and respiratory nitrate reductase activity in a mobA deletion mutant. This mutant displayed no survival defects in human monocytes or mouse lungs but failed to persist in the lungs of guinea pigs. These results implicate one or more bis-MGDdependent enzymes in the persistence of M. tuberculosis in guinea pig lungs and underscore the applicability of this animal model for assessing the role of molybdoenzymes in this pathogen.

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“…In bis-MGD, Moco is further modified by the addition of a GMP group to the phosphate of each MPT molecule. The synthesis of bis-MGD is catalyzed by MobA in a two-step reaction under GTP consumption (Reschke et al, 2013). In the first step, a bis-Mo-MPT intermediate is formed on MobA (Figure 6).…”

Section: The Attachment Of Nucleotides To Mo-mpt In Bacteriamentioning

confidence: 99%

“…In all organisms including humans, Moco is synthesized by a conserved biosynthetic pathway that can be divided into three steps, according to the stable biosynthetic intermediates which can be isolated (Figure 1) (Rajagopalan, 1996): the synthesis of cyclic pyranopterin monophosphate (cPMP) (Wuebbens and Rajagopalan, 1993), conversion of cPMP into MPT by introduction of two sulfur atoms , and insertion of molybdate to form Mo-MPT (Joshi et al, 1996). In bacteria, a fourth step may be present that includes the further modification of Mo-MPT by the addition of nucleotide monophosphates to the phosphate group of MPT, forming the bis-molybdopterin guanine dinucleotide (bis-MGD) or molybdopterin cytosine dinucleotide (MCD) cofactors (Neumann et al, 2011;Reschke et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

Leimkühler

2017

Biological Chemistry

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Abstract:The biosynthesis of the molybdenum cofactor (Moco) is a highly conserved pathway in bacteria, archaea and eukaryotes. The molybdenum atom in Mococontaining enzymes is coordinated to the dithiolene group of a tricyclic pyranopterin monophosphate cofactor. The biosynthesis of Moco can be divided into three conserved steps, with a fourth present only in bacteria and archaea:(1) formation of cyclic pyranopterin monophosphate, (2) formation of molybdopterin (MPT), (3) insertion of molybdenum into MPT to form Mo-MPT, and (4) additional modification of Mo-MPT in bacteria with the attachment of a GMP or CMP nucleotide, forming the dinucleotide variants of Moco. While the proteins involved in the catalytic reaction of each step of Moco biosynthesis are highly conserved among the Phyla, a surprising link to other cellular pathways has been identified by recent discoveries. In particular, the pathways for FeS cluster assembly and thio-modifications of tRNA are connected to Moco biosynthesis by sharing the same protein components. Further, proteins involved in Moco biosynthesis are not only shared with other pathways, but additionally have moonlighting roles. This review gives an overview of Moco biosynthesis in bacteria and humans and highlights the shared function and moonlighting roles of the participating proteins.

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Identification of a Bis-molybdopterin Intermediate in Molybdenum Cofactor Biosynthesis in Escherichia coli

Cited by 45 publications

References 48 publications

Bacterial formate hydrogenlyase complex

Bacterial formate hydrogenlyase complex

bis -Molybdopterin Guanine Dinucleotide Is Required for Persistence of Mycobacterium tuberculosis in Guinea Pigs

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

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