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FEBS J. 2014 Sep;281(18):4224-39. doi: 10.1111/febs.12784. Epub 2014 Apr 7.

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

Author information

1
Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA.

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.

DATABASES:

PDB IDs: 4HPV, 4L7I, 4K0B and 4L2Z. EC 2.5.1.6 STRUCTURED DIGITAL ABSTRACT: • sMAT and sMAT bind by x-ray crystallography (View interaction).

KEYWORDS:

S-adenosylmethionine; X-ray diffraction; enzyme engineering; methionine adenosyltransferase; natural product

PMID:
24649856
PMCID:
PMC4169312
DOI:
10.1111/febs.12784
[Indexed for MEDLINE]
Free PMC Article

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