2azt
From Proteopedia
(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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| - | [[Image:2azt.gif|left|200px]]<br /> | + | [[Image:2azt.gif|left|200px]]<br /><applet load="2azt" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2azt" size=" | + | |
caption="2azt, resolution 2.70Å" /> | caption="2azt, resolution 2.70Å" /> | ||
'''Crystal structure of H176N mutant of human Glycine N-Methyltransferase'''<br /> | '''Crystal structure of H176N mutant of human Glycine N-Methyltransferase'''<br /> | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Glycine N-methyltransferase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606628 606628]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2AZT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL, BME and CIT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycine_N-methyltransferase Glycine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.20 2.1.1.20] Full crystallographic information is available from [http:// | + | 2AZT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=BME:'>BME</scene> and <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glycine_N-methyltransferase Glycine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.20 2.1.1.20] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: glycine n-methyltransferase]] | [[Category: glycine n-methyltransferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:40:25 2008'' |
Revision as of 10:40, 23 January 2008
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Crystal structure of H176N mutant of human Glycine N-Methyltransferase
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.
About this Structure
2AZT is a Single protein structure of sequence from Homo sapiens with , and 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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