1LS3

Crystal Structure of the Complex between Rabbit Cytosolic Serine Hydroxymethyltransferase and TriGlu-5-formyl-tetrahydrofolate

Summary for 1LS3

• Entry DOI: 10.2210/pdb1ls3/pdb
• Related: 1CJ0 1DFO 1EJI 1KL2
• Descriptor: Serine Hydroxymethyltransferase, PYRIDOXAL-5'-PHOSPHATE, GLYCINE, ... (6 entities in total)
• Functional Keywords: asymmetric tetramer, transferase
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Cytoplasm: p07511
• Total number of polymer chains: 4
• Total formula weight: 214634.86

Authors

Fu, T.F.,Scarsdale, J.N.,Kazanina, G.,Schirch, V.,Wright, H.T. (deposition date: 2002-05-16, release date: 2003-02-04, Last modification date: 2024-04-03)

Primary citation

Fu, T.F.,Scarsdale, J.N.,Kazanina, G.,Schirch, V.,Wright, H.T.
Location of the Pteroylpolyglutamate Binding Site on Rabbit Cytosolic Serine Hydroxymethyltransferase
J.Biol.Chem., 278:2645-2653, 2003

PubMed Abstract: Serine hydroxymethyltransferase (SHMT; EC 2.1.2.1) catalyzes the reversible interconversion of serine and glycine with transfer of the serine side chain one-carbon group to tetrahydropteroylglutamate (H(4)PteGlu), and also the conversion of 5,10-methenyl-H(4)PteGlu to 5-formyl-H(4)PteGlu. In the cell, H(4)PteGlu carries a poly-gamma-glutamyl tail of at least 3 glutamyl residues that is required for physiological activity. This study combines solution binding and mutagenesis studies with crystallographic structure determination to identify the extended binding site for tetrahydropteroylpolyglutamate on rabbit cytosolic SHMT. Equilibrium binding and kinetic measurements of H(4)PteGlu(3) and H(4)PteGlu(5) with wild-type and Lys --> Gln or Glu site mutant homotetrameric rabbit cytosolic SHMTs identified lysine residues that contribute to the binding of the polyglutamate tail. The crystal structure of the enzyme in complex with 5-formyl-H(4)PteGlu(3) confirms the solution data and indicates that the conformation of the pteridine ring and its interactions with the enzyme differ slightly from those observed in complexes of the monoglutamate cofactor. The polyglutamate chain, which does not contribute to catalysis, exists in multiple conformations in each of the two occupied binding sites and appears to be bound by the electrostatic field created by the cationic residues, with only limited interactions with specific individual residues.

PubMed: 12438316
DOI: 10.1074/jbc.M210649200

Experimental method

X-RAY DIFFRACTION (2.7 Å)