2AZT
Crystal structure of H176N mutant of human Glycine N-Methyltransferase
Summary for 2AZT
Entry DOI | 10.2210/pdb2azt/pdb |
Related | 1R74 |
Descriptor | Glycine N-methyltransferase, BETA-MERCAPTOETHANOL, CITRIC ACID, ... (5 entities in total) |
Functional Keywords | glycine n-methyltransferase, transferase |
Biological source | Homo sapiens (human) |
Cellular location | Cytoplasm: Q14749 |
Total number of polymer chains | 2 |
Total formula weight | 66330.79 |
Authors | Luka, Z.,Pakhomova, S.,Luka, Y.,Newcomer, M.E.,Wagner, C. (deposition date: 2005-09-12, release date: 2006-09-26, Last modification date: 2023-08-23) |
Primary citation | Luka, Z.,Pakhomova, S.,Luka, Y.,Newcomer, M.E.,Wagner, C. Destabilization of human glycine N-methyltransferase by H176N mutation. Protein Sci., 16:1957-1964, 2007 Cited by PubMed Abstract: 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. PubMed: 17660255DOI: 10.1110/ps.072921507 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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