Abstract
Methionine adenosyltransferase (MAT) is a family of enzymes that utilizes ATP and methionine to produce S-adenosylmethionine (AdoMet), the most crucial methyl donor in the biological methylation of biomolecules and bioactive natural products. Here, we report that the MAT from Sulfolobus solfataricus (sMAT), an enzyme from a poorly explored class of the MAT family, has the ability to produce a range of differentially alkylated AdoMet analogs in the presence of non-native methionine analogs and ATP. To investigate the molecular basis for AdoMet analog production, we have crystallized the sMAT in the AdoMet bound, S-adenosylethionine (AdoEth) bound and unbound forms. Notably, among these structures, the AdoEth bound form offers the first MAT structure containing a non-native product, and cumulatively these structures add new structural insight into the MAT family and allow for detailed active site comparison with its homologs in Escherichia coli and human. As a thermostable MAT structure from archaea, the structures herein also provide a basis for future engineering to potentially broaden AdoMet analog production as reagents for methyltransferase-catalyzed 'alkylrandomization' and/or the study of methylation in the context of biological processes.
Original language | English |
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Pages (from-to) | 4224-4239 |
Number of pages | 16 |
Journal | FEBS Journal |
Volume | 281 |
Issue number | 18 |
DOIs | |
State | Published - Sep 1 2014 |
Bibliographical note
Publisher Copyright:© 2014 FEBS.
Keywords
- S-adenosylmethionine
- X-ray diffraction
- enzyme engineering
- methionine adenosyltransferase
- natural product
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology