title: Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus.
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.
  
  
  METHODS
  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).
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Wang
authors.forename: Shanteri
authors.initials: S
authors.lastname: Singh
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Huber
authors.forename: Kate E
authors.initials: KE
authors.lastname: Helmich
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hurley
authors.forename: Randal D
authors.initials: RD
authors.lastname: Goff
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bingman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
authors.forename: George N
authors.initials: GN
authors.lastname: Phillips
mesh_terms: D020816:Amino Acid Motifs; D019843:Archaeal Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D007700:Kinetics; D008715:Methionine / Q000737:chemistry; D008716:Methionine Adenosyltransferase / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D013379:Substrate Specificity; D048229:Sulfolobus solfataricus / Q000201:enzymology*
chemical_list: D019843:Archaeal Proteins; D008715:Methionine; D008716:Methionine Adenosyltransferase
keywords: S-adenosylmethionine; X-ray diffraction; enzyme engineering; methionine adenosyltransferase; natural product