Identification of a 5'-Deoxyadenosine Deaminase in Methanocaldococcus jannaschii and Its Possible Role in Recycling the Radical S-Adenosylmethionine Enzyme Reaction Product 5'-Deoxyadenosine

Miller, Danielle; O’Brien, Kaitlin M.; Xu, Huimin; White, Robert H.

doi:10.1128/jb.01308-13

Cited by 23 publications

(29 citation statements)

References 28 publications

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“…We can propose that, more often than not, the first steps of 5′‐dAdo degradation will proceed by a futalosine/MSP moonlighting pathway. This is substantiated by the presence of a 5′‐dAdo deaminase in this same organism (Miller et al ., ). MtiP is active with six different purine nucleosides, including forms containing hypoxanthine and therefore able to participate in the MSP, in menaquinone synthesis and in 5′‐dAdo phosphorolysis, possibly after deamination into 5′‐deoxyinosine, as well as in general purine salvage.…”

Section: ′‐Deoxyadenosine Metabolism As a Paralogous Pathway Of The Mspmentioning

confidence: 97%

Revisiting the methionine salvage pathway and its paralogues

Sekowska

Ashida

Danchin

2018

Microbial Biotechnology

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SummaryMethionine is essential for life. Its chemistry makes it fragile in the presence of oxygen. Aerobic living organisms have selected a salvage pathway (the MSP) that uses dioxygen to regenerate methionine, associated to a ratchet‐like step that prevents methionine back degradation. Here, we describe the variation on this theme, developed across the tree of life. Oxygen appeared long after life had developed on Earth. The canonical MSP evolved from ancestors that used both predecessors of ribulose bisphosphate carboxylase oxygenase (RuBisCO) and methanethiol in intermediate steps. We document how these likely promiscuous pathways were also used to metabolize the omnipresent by‐products of S‐adenosylmethionine radical enzymes as well as the aromatic and isoprene skeleton of quinone electron acceptors.

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Section: ′‐Deoxyadenosine Metabolism As a Paralogous Pathway Of The Mspmentioning

confidence: 97%

Revisiting the methionine salvage pathway and its paralogues

Sekowska

Ashida

Danchin

2018

Microbial Biotechnology

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“…The MonoQ fractions containing Wt MJ1459‐, C127S MJ1459‐, and MJ1655‐derived proteins were identified by SDS‐PAGE analysis of the individual fractions. The protein bands corresponding to the predicted molecular mass of the MJ1459 gene product (∼62 kDa) and MJ1655 (∼20 kDa) were excised from the polyacrylamide gel, and the cut gel bands were prepared for matrix assisted laser desorption ionization mass spectrometry (MALDI‐MS) as described previously …”

Section: Methodsmentioning

confidence: 99%

“…The protein bands corresponding to the predicted molecular mass of the MJ1459 gene product (62 kDa) and MJ1655 (20 kDa) were excised from the polyacrylamide gel, and the cut gel bands were prepared for matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) as described previously. 15 C127A Ade was not efficiently recombinantly expressed in E. coli as judged by SDS-PAGE of the total cellular protein, and the C127A MJ1459-gene product was unable to be identified by MALDI-MS (Supporting Information Fig. S2).…”

Section: Cloning Overexpression and Purification Of The Mj1459 (Wt mentioning

confidence: 99%

Purine salvage in Methanocaldococcus jannaschii: Elucidating the role of a conserved cysteine in adenine deaminase

Miller

Bevan

et al. 2016

Proteins

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Adenine deaminases (Ade) and hypoxanthine/guanine phosphoribosyltransferases (Hpt) are widely distributed enzymes involved in purine salvage. Characterization of the previously uncharacterized Ade (MJ1459 gene product) and Hpt (MJ1655 gene product) are discussed here and provide insight into purine salvage in Methanocaldococcus jannaschii. Ade was demonstrated to use either Fe(II) and/or Mn(II) as the catalytic metal. Hpt demonstrated no detectable activity with adenine, but was equally specific for hypoxanthine and guanine with a kcat /KM of 3.2 × 10(7) and 3.0 × 10(7) s(- 1) M(- 1) , respectively. These results demonstrate that hypoxanthine and IMP are the central metabolites in purine salvage in M. jannaschii for AMP and GMP production. A conserved cysteine (C127, M. jannaschii numbering) was examined due to its high conservation in bacterial and archaeal homologues. To assess the role of this highly conserved cysteine in M. jannaschii Ade, site-directed mutagenesis was performed. It was determined that mutation to serine (C127S) completely abolished Ade activity and mutation to alanine (C127A) exhibited 10-fold decrease in kcat over the wild type Ade. To further investigate the role of C127, detailed molecular docking and dynamics studies were performed and revealed adenine was unable to properly orient in the active site in the C127A and C127S Ade model structures due to distinct differences in active site conformation and rotation of D261. Together this work illuminates purine salvage in M. jannaschii and the critical role of a cysteine residue in maintaining active site conformation of Ade. Proteins 2016; 84:828-840. © 2016 Wiley Periodicals, Inc.

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“…5). The identities of the purified proteins were also confirmed by matrix-assisted laser desorption ionization-MS analysis of the tryptic digested protein band from the SDS gel based on a previously described procedure (18).…”

Section: M/z and (M ϫ H) ϫ ϭ 3694 M/z Tandem Ms (Ms/ms) Of The (M ϫ H)mentioning

confidence: 99%

Identification of the Final Two Genes Functioning in Methanofuran Biosynthesis in Methanocaldococcus jannaschii

Wang

Jones

et al. 2015

J Bacteriol

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All methanofuran structural variants contain a basic core structure of 4-[N-(␥-L-glutamyl)-p-(␤-aminoethyl)phenoxymethyl]-(aminomethyl)furan (APMF-Glu) but have different side chains depending on the source organism. Recently, we identified four genes (MfnA, MfnB, MfnC, and MfnD) that are responsible for the biosynthesis of the methanofuran precursor ␥-glutamyltyramine and 5-(aminomethyl)-3-furanmethanol-phosphate (F1-P) from tyrosine, glutamate, glyceraldehyde-3-P, and alanine in Methanocaldococcus jannaschii. How ␥-glutamyltyramine and F1-P couple together to form the core structure of methanofuran was previously unknown. Here, we report the identification of two enzymes encoded by the genes mj0458 and mj0840 that catalyze the formation of F1-PP from ATP and F1-P and the condensation of F1-PP with ␥-glutamyltyramine, respectively, to form APMF-Glu. We have annotated these enzymes as MfnE and MfnF, respectively, representing the fifth and sixth enzymes in the methanofuran biosynthetic pathway to be identified. Although MfnE was previously reported as an archaeal adenylate kinase, our present results show that MfnE is a promiscuous enzyme and that its possible physiological role is to produce F1-PP. Unlike other enzymes catalyzing coupling reactions involving pyrophosphate as the leaving group, MfnF exhibits a distinctive ␣/␤ twolayer sandwich structure. By comparing MfnF with thiamine synthase and dihydropteroate synthase, a substitution nucleophilic unimolecular (S N -1) reaction mechanism is proposed for MfnF. With the identification of MfnE and MfnF, the biosynthetic pathway for the methanofuran core structure APMF-Glu is complete. IMPORTANCEThis work describes the identification of the final two enzymes responsible for catalyzing the biosynthesis of the core structure of methanofuran. The gene products of mj0458 and mj0840 catalyze the formation of F1-PP and the coupling of F1-PP with ␥-glutamyltyramine, respectively, to form APMF-Glu. Although the chemistry of such a coupling reaction is widespread in biochemistry, we provide here the first evidence that such a mechanism is used in methanofuran biosynthesis. MfnF belongs to the hydantoinase A family (PF01968) and exhibits a unique ␣/␤ two-layer sandwich structure that is different from the enzymes catalyzing similar reactions. Our results show that MfnF catalyzes the formation of an ether bond during methanofuran biosynthesis. Therefore, this work further expands the functionality of this enzyme family. Methanofuran is the first in a series of coenzymes involved in the biochemical reduction of carbon dioxide to methane (1-3). This process, known as methanogenesis, is carried out only by the methanogenic archaea, which produce more than 400 million tons of methane each year as an essential part of the global carbon cycle (4). Methanofuran is the initial C 1 acceptor molecule involved in the first two-electron reduction of carbon dioxide to produce the formamide derivative of methanofuran, where the formate is attached to the amino group of methanofu...

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Identification of a 5'-Deoxyadenosine Deaminase in Methanocaldococcus jannaschii and Its Possible Role in Recycling the Radical S-Adenosylmethionine Enzyme Reaction Product 5'-Deoxyadenosine

Cited by 23 publications

References 28 publications

Revisiting the methionine salvage pathway and its paralogues

Revisiting the methionine salvage pathway and its paralogues

Purine salvage in Methanocaldococcus jannaschii: Elucidating the role of a conserved cysteine in adenine deaminase

Identification of the Final Two Genes Functioning in Methanofuran Biosynthesis in Methanocaldococcus jannaschii

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