4HPV

Crystal structure of S-Adenosylmethionine synthetase from Sulfolobus solfataricus

Summary for 4HPV

• Entry DOI: 10.2210/pdb4hpv/pdb
• Related: 4K0B 4L2Z 4L7I
• Descriptor: S-adenosylmethionine synthase (2 entities in total)
• Functional Keywords: structural genomics, psi-biology, protein structure initiative, enzyme discovery for natural product biosynthesis, natpro, transferase
• Biological source: Sulfolobus solfataricus
• Total number of polymer chains: 2
• Total formula weight: 90661.37

Authors

Wang, F.,Hurley, K.A.,Helmich, K.E.,Singh, S.,Bingman, C.A.,Thorson, J.S.,Phillips Jr., G.N.,Enzyme Discovery for Natural Product Biosynthesis (NatPro) (deposition date: 2012-10-24, release date: 2012-11-14, Last modification date: 2017-11-15)

Primary citation

Wang, F.,Singh, S.,Zhang, J.,Huber, T.D.,Helmich, K.E.,Sunkara, M.,Hurley, K.A.,Goff, R.D.,Bingman, C.A.,Morris, A.J.,Thorson, J.S.,Phillips, G.N.
Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus.
Febs J., 281:4224-4239, 2014

PubMed 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.

PubMed: 24649856
DOI: 10.1111/febs.12784

Experimental method

X-RAY DIFFRACTION (2.214 Å)