Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus

Fengbin Wang, Shanteri Singh, Jianjun Zhang, Tyler D. Huber, Kate E. Helmich, Manjula Sunkara, Katherine A. Hurley, Randal D. Goff, Craig A. Bingman, Andrew J. Morris, Jon S. Thorson, George N. Phillips

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 languageEnglish
Pages (from-to)4224-4239
Number of pages16
JournalFEBS Journal
Volume281
Issue number18
DOIs
StatePublished - 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

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