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| | <StructureSection load='2azt' size='340' side='right'caption='[[2azt]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='2azt' size='340' side='right'caption='[[2azt]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2azt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AZT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2azt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AZT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1r74|1r74]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNMT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glycine_N-methyltransferase Glycine N-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.20 2.1.1.20] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2azt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2azt OCA], [https://pdbe.org/2azt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2azt RCSB], [https://www.ebi.ac.uk/pdbsum/2azt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2azt ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2azt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2azt OCA], [https://pdbe.org/2azt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2azt RCSB], [https://www.ebi.ac.uk/pdbsum/2azt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2azt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/GNMT_HUMAN GNMT_HUMAN]] Defects in GNMT are the cause of glycine N-methyltransferase deficiency (GNMT deficiency) [MIM:[https://omim.org/entry/606664 606664]]; also known as hypermethioninemia. The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases.
| + | [https://www.uniprot.org/uniprot/GNMT_HUMAN GNMT_HUMAN] Defects in GNMT are the cause of glycine N-methyltransferase deficiency (GNMT deficiency) [MIM:[https://omim.org/entry/606664 606664]; also known as hypermethioninemia. The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GNMT_HUMAN 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.<ref>PMID:15340920</ref> <ref>PMID:17660255</ref>
| + | [https://www.uniprot.org/uniprot/GNMT_HUMAN 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.<ref>PMID:15340920</ref> <ref>PMID:17660255</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glycine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Luka, Y]] | + | [[Category: Luka Y]] |
| - | [[Category: Luka, Z]] | + | [[Category: Luka Z]] |
| - | [[Category: Newcomer, M E]] | + | [[Category: Newcomer ME]] |
| - | [[Category: Pakhomova, S]] | + | [[Category: Pakhomova S]] |
| - | [[Category: Wagner, C]] | + | [[Category: Wagner C]] |
| - | [[Category: Glycine n-methyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pakhomova S, Luka Z, Grohmann S, Wagner C, Newcomer ME. Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes. Proteins. 2004 Nov 1;57(2):331-7. PMID:15340920 doi:10.1002/prot.20209
- ↑ Luka Z, Pakhomova S, Luka Y, Newcomer ME, Wagner C. Destabilization of human glycine N-methyltransferase by H176N mutation. Protein Sci. 2007 Sep;16(9):1957-64. Epub 2007 Jul 27. PMID:17660255 doi:10.1110/ps.072921507
- ↑ Luka Z, Pakhomova S, Luka Y, Newcomer ME, Wagner C. Destabilization of human glycine N-methyltransferase by H176N mutation. Protein Sci. 2007 Sep;16(9):1957-64. Epub 2007 Jul 27. PMID:17660255 doi:10.1110/ps.072921507
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