Binding of S-methyl-5'-thioadenosine and S-adenosyl-L-methionine to protein MJ0100 triggers an open-to-closed conformational change in its CBS motif pair

J Mol Biol. 2010 Feb 26;396(3):800-20. doi: 10.1016/j.jmb.2009.12.012. Epub 2009 Dec 21.


Cystathionine beta-synthase (CBS) domains are small motifs that are present in proteins with completely different functions. Several genetic diseases in humans have been associated with mutations in their sequence, which has made them promising targets for rational drug design. The protein MJ0100 from Methanocaldococcus jannaschii includes a DUF39 domain of so far unknown function and a CBS domain pair (Bateman domain) at its C-terminus. This work presents the crystallographic analysis of four different states of the CBS motif pair of MJ0100 in complex with different numbers of S-adenosyl-L-methionine (SAM) and S-methyl-5'-thioadenosine (MTA) ligands, providing evidence that ligand-induced conformational reorganization of Bateman domain dimers could be an important regulatory mechanism. These observations are in contrast to what is known from most of the other Bateman domain structures but are supported by recent studies on the magnesium transporter MgtE. Our structures represent the first example of a CBS domain protein complexed with SAM and/or MTA and might provide a structural basis for understanding the molecular mechanisms regulated by SAM upon binding to the C-terminal domain of human CBS, whose structure remains unknown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Allosteric Regulation
  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Methanococcales / enzymology*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • S-Adenosylmethionine / metabolism*
  • Sequence Alignment
  • Thionucleosides / metabolism*


  • Archaeal Proteins
  • Thionucleosides
  • S-methyl-5'-methylthioadenosine
  • S-Adenosylmethionine
  • Adenosine

Associated data

  • PDB/3KPB
  • PDB/3KPC
  • PDB/3KPD