View source for 2azt


==Crystal structure of H176N mutant of human Glycine N-Methyltransferase==
<StructureSection load='2azt' size='340' side='right'caption='[[2azt]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</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='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>
== 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.
== 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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/az/2azt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2azt ConSurf].
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== 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<ref>PMID:17660255</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2azt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Luka Y]]
[[Category: Luka Z]]
[[Category: Newcomer ME]]
[[Category: Pakhomova S]]
[[Category: Wagner C]]