ArticleAnalytical biochemistry2014
A sensitive mass spectrum assay to characterize engineered methionine adenosyltransferases with S-alkyl methionine analogues as substrates.
Article in Analytical biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Selective chemical tracking of DNA methylomes in live cells.Epigenomics · 2025Article
- Engineered Methionine Adenosyltransferase Cascades for Metabolic Labeling of Individual DNA Methylomes in Live Cells.Journal of the American Chemical Society · 2024Article
- Visible-Light Removable Photocaging Groups Accepted by MjMAT Variant: Structural Basis and Compatibility with DNA and RNA Methyltransferases.Chembiochem : a European journal of chemical biology · 2022Article
- Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.JACS Au · 2021Article
- Profiling and Validation of Live-Cell Protein Methylation with Engineered Enzymes and Methionine Analogues.Current protocols · 2021Article
- Methylation of dual-specificity phosphatase 4 controls cell differentiation.Cell reports · 2021Article
- Engineered SAM Synthetases for Enzymatic Generation of AdoMet Analogs with Photocaging Groups and Reversible DNA Modification in Cascade Reactions.Angewandte Chemie (International ed. in English) · 2021Article
- Nucleoside-modified AdoMet analogues for differential methyltransferase targeting.Chemical communications (Cambridge, England) · 2020Article
- A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion.eLife · 2019Article
- In-Cell Synthesis of Bioorthogonal Alkene Tag S-Allyl-Homocysteine and Its Coupling with Reprogrammed Translation.International journal of molecular sciences · 2019Article
- Construction of Fluorescent Analogs to Follow the Uptake and Distribution of Cobalamin (Vitamin BCell chemical biology · 2018Article
- Chemical and Biochemical Perspectives of Protein Lysine Methylation.Chemical reviews · 2018Review
- Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis.Science (New York, N.Y.) · 2018Article
- Large-scale, protection-free synthesis of Se-adenosyl-L-selenomethionine analogues and their application as cofactor surrogates of methyltransferases.Organic letters · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Methionine adenosyltransferases (MATs) catalyze the formation of S-adenosyl-l-methionine (SAM) inside living cells. Recently, S-alkyl analogues of SAM have been documented as cofactor surrogates to label novel targets of methyltransferases. However, these chemically synthesized SAM analogues are not suitable for cell-based studies because of their poor membrane permeability. This issue was recently addressed under a cellular setting through a chemoenzymatic strategy to process membrane-permeable S-alkyl analogues of methionine (SAAMs) into the SAM analogues with engineered MATs. Here we describe a general sensitive activity assay for engineered MATs by converting the reaction products into S-alkylthioadenosines, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) quantification. With this assay, 40 human MAT mutants were evaluated against 7 SAAMs as potential substrates. The structure-activity relationship revealed that, besides better engaged SAAM binding by the MAT mutants (lower Km value in contrast to native MATs), the gained activity toward the bulky SAAMs stems from their ability to maintain the desired linear SN2 transition state (reflected by higher kcat value). Here the I117A mutant of human MATI was identified as the most active variant for biochemical production of SAM analogues from diverse SAAMs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.