A subfamily of PLP-dependent enzymes specialized in handling terminal amines

Schiroli, Davide; Peracchi, Alessio

doi:10.1016/j.bbapap.2015.02.023

Cited by 65 publications

(71 citation statements)

References 108 publications

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“…Most omega aminotransferases are PLP-fold type I enzymes that catalyze the transfer of an amino group from a β-, γ- or other ω-amino acid or an amine to pyruvate or α-ketoglutarate (Schiroli and Peracchi 2015). In order to confirm the presence of 6-ACA ω-aminotransferase activity in P. jessenii GO3, a protein extract of caprolactam-induced cells was prepared and incubated with 6-ACA and pyruvate or α-ketoglutarate, and levels of 6-ACA and produced alanine or glutamate were determined using OPA derivatization and HPLC.…”

Section: Resultsmentioning

confidence: 99%

“…BLAST searches using the protein sequence of the Pj AT demonstrated relatedness to the fold-type I PLP enzymes, more in particular to the subgroup II aminotransferases, which are now often grouped as class III aminotransferases (Schiroli and Peracchi 2015; Steffen-Munsberg et al 2015). These enzymes catalyze conversion of ω-amino acids to aldehydes (EC 2.6.1.18).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the caprolactam degradation pathway in Pseudomonas jessenii using mass spectrometry-based proteomics

Otzen

Palacio

Janssen

2018

Appl Microbiol Biotechnol

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Some bacterial cultures are capable of growth on caprolactam as sole carbon and nitrogen source, but the enzymes of the catabolic pathway have not been described. We isolated a caprolactam-degrading strain of Pseudomonas jessenii from soil and identified proteins and genes putatively involved in caprolactam metabolism using quantitative mass spectrometry-based proteomics. This led to the discovery of a caprolactamase and an aminotransferase that are involved in the initial steps of caprolactam conversion. Additionally, various proteins were identified that likely are involved in later steps of the pathway. The caprolactamase consists of two subunits and demonstrated high sequence identity to the 5-oxoprolinases. Escherichia coli cells expressing this caprolactamase did not convert 5-oxoproline but were able to hydrolyze caprolactam to form 6-aminocaproic acid in an ATP-dependent manner. Characterization of the aminotransferase revealed that the enzyme deaminates 6-aminocaproic acid to produce 6-oxohexanoate with pyruvate as amino acceptor. The amino acid sequence of the aminotransferase showed high similarity to subgroup II ω-aminotransferases of the PLP-fold type I proteins. Finally, analyses of the genome sequence revealed the presence of a caprolactam catabolism gene cluster comprising a set of genes involved in the conversion of caprolactam to adipate.Electronic supplementary materialThe online version of this article (10.1007/s00253-018-9073-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of the caprolactam degradation pathway in Pseudomonas jessenii using mass spectrometry-based proteomics

Otzen

Palacio

Janssen

2018

Appl Microbiol Biotechnol

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“…Most of these enzymes are ω-aminotransferases, with specific features explained by a number of conserved residues in the active site [56,57]. Six crystal structures of the human OAT enzyme are present in the PDB databank: one of the recombinant enzymes [12], and three enzyme complexes with 5FMOrn [58], l -canaline and gabaguline [59], rerspectively, and two forms mutated on one or three residues [60].…”

Section: Structure Of Oatmentioning

confidence: 99%

Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

Ginguay

Cynober

Curis

et al. 2017

Biology

101

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Ornithine δ-aminotransferase (OAT, E.C. 2.6.1.13) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines. It is also involved in proline (Pro) synthesis. Deficiency in OAT causes gyrate atrophy, a rare but serious inherited disease, a further measure of the importance of this enzyme.

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“…HPLC analysis of reaction mixtures in which OA and glyoxylate-which has the advantage of binding quite weakly to glutamine transaminase K, limiting the phenomenon of substrate inhibition observed with larger α-keto acid substrates (25,26)-were incubated overnight with KYAT1 indicated the appearance of two peaks corresponding to dOA (SI Appendix, Figs. S7B and S8).…”

Section: Formation Of Dgsh Is a Side Reaction Of Numerous Transaminasesmentioning

confidence: 99%

Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione

Peracchi

Veiga‐da‐Cunha

Kuhara

et al. 2017

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

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The mammalian gene Nit1 (nitrilase-like protein 1) encodes a protein that is highly conserved in eukaryotes and is thought to act as a tumor suppressor. Despite being ∼35% sequence identical to ω-amidase (Nit2), the Nit1 protein does not hydrolyze efficiently α-ketoglutaramate (a known physiological substrate of Nit2), and its actual enzymatic function has so far remained a puzzle. In the present study, we demonstrate that both the mammalian Nit1 and its yeast ortholog are amidases highly active toward deaminated glutathione (dGSH; i.e., a form of glutathione in which the free amino group has been replaced by a carbonyl group). We further show that Nit1-KO mutants of both human and yeast cells accumulate dGSH and the same compound is excreted in large amounts in the urine of Nit1-KO mice. Finally, we show that several mammalian aminotransferases (transaminases), both cytosolic and mitochondrial, can form dGSH via a common (if slow) side-reaction and provide indirect evidence that transaminases are mainly responsible for dGSH formation in cultured mammalian cells. Altogether, these findings delineate a typical instance of metabolite repair, whereby the promiscuous activity of some abundant enzymes of primary metabolism leads to the formation of a useless and potentially harmful compound, which needs a suitable "repair enzyme" to be destroyed or reconverted into a useful metabolite. The need for a dGSH repair reaction does not appear to be limited to eukaryotes: We demonstrate that Nit1 homologs acting as excellent dGSH amidases also occur in Escherichia coli and other glutathione-producing bacteria.metabolite repair | deaminated glutathione | amidase | aminotransferases

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A subfamily of PLP-dependent enzymes specialized in handling terminal amines

Cited by 65 publications

References 108 publications

Characterization of the caprolactam degradation pathway in Pseudomonas jessenii using mass spectrometry-based proteomics

Characterization of the caprolactam degradation pathway in Pseudomonas jessenii using mass spectrometry-based proteomics

Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione

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