2azt
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(New page: 200px<br /> <applet load="2azt" size="450" color="white" frame="true" align="right" spinBox="true" caption="2azt, resolution 2.70Å" /> '''Crystal structure o...)
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Revision as of 18:50, 12 November 2007
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Crystal structure of H176N mutant of human Glycine N-Methyltransferase
Contents |
Overview
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.
Disease
Known disease associated with this structure: Glycine N-methyltransferase deficiency OMIM:[606628]
About this Structure
2AZT is a Single protein structure of sequence from Homo sapiens with CL, BME and CIT as ligands. Active as Glycine N-methyltransferase, with EC number 2.1.1.20 Full crystallographic information is available from OCA.
Reference
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
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