Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode

J Biol Chem. 2020 Mar 13;295(11):3708-3718. doi: 10.1074/jbc.RA119.012256. Epub 2020 Feb 2.


Management of the agricultural pathogen soybean cyst nematode (SCN) relies on the use of SCN-resistant soybean cultivars, a strategy that has been failing in recent years. An underutilized source of resistance in the soybean genotype Peking is linked to two polymorphisms in serine hydroxy-methyltransferase 8 (SHMT8). SHMT is a pyridoxal 5'-phosphate-dependent enzyme that converts l-serine and (6S)-tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate. Here, we determined five crystal structures of the 1884-residue SHMT8 tetramers from the SCN-susceptible cultivar (cv.) Essex and the SCN-resistant cv. Forrest (whose resistance is derived from the SHMT8 polymorphisms in Peking); the crystal structures were determined in complex with various ligands at 1.4-2.35 Å resolutions. We find that the two Forrest-specific polymorphic substitutions (P130R and N358Y) impact the mobility of a loop near the entrance of the (6S)-tetrahydrofolate-binding site. Ligand-binding and kinetic studies indicate severely reduced affinity for folate and dramatically impaired enzyme activity in Forrest SHMT8. These findings imply widespread effects on folate metabolism in soybean cv. Forrest that have implications for combating the widespread increase in virulent SCN.

Keywords: Glycine max; X-ray crystallography; disease resistance; enzyme; folate; host-pathogen interaction; ligand-binding protein; plant defense; quantitative trait loci (QTL); serine hydroxymethyltransferase 8 (SHMT8); soybean cyst nematode.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Conserved Sequence
  • Disease Resistance*
  • Folic Acid / metabolism*
  • Glycine Hydroxymethyltransferase / chemistry
  • Glycine Hydroxymethyltransferase / metabolism*
  • Kinetics
  • Ligands
  • Models, Biological
  • Models, Molecular
  • Nematoda / physiology*
  • Plant Diseases / parasitology*
  • Plant Proteins / chemistry
  • Plant Proteins / metabolism*
  • Pyridoxal Phosphate / metabolism
  • Soybeans / enzymology*
  • Static Electricity
  • Structural Homology, Protein
  • Tetrahydrofolates / chemistry
  • Tetrahydrofolates / metabolism


  • Ligands
  • Plant Proteins
  • Tetrahydrofolates
  • 5,6,7,8-tetrahydrofolic acid
  • Pyridoxal Phosphate
  • Folic Acid
  • Glycine Hydroxymethyltransferase

Associated data

  • PDB/6CCZ
  • PDB/6FL5
  • PDB/5V7I
  • PDB/1DFO
  • PDB/1EQB
  • PDB/1EJI
  • PDB/1KL2
  • PDB/1LS3
  • PDB/2VMY
  • PDB/4OYT
  • PDB/6SMW
  • PDB/1CJ0
  • PDB/6UXH
  • PDB/6UXI
  • PDB/6UXJ
  • PDB/6UXK
  • PDB/6UXL