3thr | pdb_00003thr

Crystal structure of rat native liver Glycine N-methyltransferase complexed with 5-methyltetrahydrofolate monoglutamate

spinqualitylabelsall models 3thr, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3thr is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: ACE, C2F, TAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GNMT_RAT Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine. Publication Abstract from PubMed Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. In mammalian liver it reduces S-adenosylmethionine levels by using it to methylate glycine, producing N-methylglycine (sarcosine) and S-adenosylhomocysteine. GNMT is inhibited by binding two molecules of 5-methyltetrahydrofolate (mono- or polyglutamate forms) per tetramer of the active enzyme. Inhibition is sensitive to the status of the N-terminal valine of GNMT and to polyglutamation of the folate inhibitor. It is inhibited by pentaglutamate form more efficiently compared to monoglutamate form. The native rat liver GNMT contains an acetylated N-terminal valine and is inhibited much more efficiently compared to the recombinant protein expressed in E. coli where the N-terminus is not acetylated. In this work we used a protein crystallography approach to evaluate the structural basis for these differences. We show that in the folate-GNMT complexes with the native enzyme, two folate molecules establish three and four hydrogen bonds with the protein. In the folate-recombinant GNMT complex only one hydrogen bond is established. This difference results in more effective inhibition by folate of the native liver GNMT activity compared to the recombinant enzyme. Differences in folate-protein interactions result in differing inhibition of native rat liver and recombinant glycine N-methyltransferase by 5-methyltetrahydrofolate.,Luka Z, Pakhomova S, Loukachevitch LV, Newcomer ME, Wagner C Biochim Biophys Acta. 2011 Oct 20. PMID:22037183 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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