1ls3
From Proteopedia
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Crystal Structure of the Complex between Rabbit Cytosolic Serine Hydroxymethyltransferase and TriGlu-5-formyl-tetrahydrofolate
Overview
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.
About this Structure
1LS3 is a Single protein structure of sequence from Oryctolagus cuniculus with PLP, PLP, TGF and GOL as ligands. Active as Glycine hydroxymethyltransferase, with EC number 2.1.2.1 Full crystallographic information is available from OCA.
Reference
Location of the pteroylpolyglutamate-binding site on rabbit cytosolic serine hydroxymethyltransferase., Fu TF, Scarsdale JN, Kazanina G, Schirch V, Wright HT, J Biol Chem. 2003 Jan 24;278(4):2645-53. Epub 2002 Nov 15. PMID:12438316
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