2azt | pdb_00002azt

Crystal structure of H176N mutant of human Glycine N-Methyltransferase

spinqualitylabelsall models 2azt, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2azt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: BME, CIT, CL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GNMT_HUMAN Defects in GNMT are the cause of glycine N-methyltransferase deficiency (GNMT deficiency) [MIM:606664; also known as hypermethioninemia. The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases. Function GNMT_HUMAN 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed In the presence of moderate (2-4 M) urea concentrations the tetrameric enzyme, glycine N-methyltransferase (GNMT), dissociates into compact monomers. Higher concentrations of urea (7-8 M) promote complete denaturation of the enzyme. We report here that the H176N mutation in this enzyme, found in humans with hypermethioninaemia, significantly decreases stability of the tetramer, although H176 is located far from the intersubunit contact areas. Dissociation of the tetramer to compact monomers and unfolding of compact monomers of the mutant protein were detected by circular dichroism, quenching of fluorescence emission, size-exclusion chromatography, and enzyme activity. The values of apparent free energy of dissociation of tetramer and of unfolding of compact monomers for the H176N mutant (27.7 and 4.2 kcal/mol, respectively) are lower than those of wild-type protein (37.5 and 6.2 kcal/mol). A 2.7 A resolution structure of the mutant protein revealed no significant difference in the conformation of the protein near the mutated residue. Destabilization of human glycine N-methyltransferase by H176N mutation.,Luka Z, Pakhomova S, Luka Y, Newcomer ME, Wagner C Protein Sci. 2007 Sep;16(9):1957-64. Epub 2007 Jul 27. PMID:17660255 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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