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| - | [[Image:1d2c.gif|left|200px]] | |
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| - | {{Structure
| + | ==METHYLTRANSFERASE== |
| - | |PDB= 1d2c |SIZE=350|CAPTION= <scene name='initialview01'>1d2c</scene>, resolution 2.5Å
| + | <StructureSection load='1d2c' size='340' side='right'caption='[[1d2c]], [[Resolution|resolution]] 2.50Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[1d2c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D2C FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[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] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | |GENE=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1d2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d2c OCA], [https://pdbe.org/1d2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d2c RCSB], [https://www.ebi.ac.uk/pdbsum/1d2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d2c ProSAT]</span></td></tr> |
| - | |DOMAIN=
| + | </table> |
| - | |RELATEDENTRY=[[1d2g|1D2G]], [[1d2h|1D2H]]
| + | == Function == |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d2c OCA], [http://www.ebi.ac.uk/pdbsum/1d2c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d2c RCSB]</span>
| + | [https://www.uniprot.org/uniprot/GNMT_RAT GNMT_RAT] 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. |
| - | }}
| + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | '''METHYLTRANSFERASE'''
| + | Check<jmol> |
| - | | + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d2/1d2c_consurf.spt"</scriptWhenChecked> |
| - | ==Overview== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | Glycine N-methyltransferase (S-adenosyl-l-methionine: glycine methyltransferase, EC 2.1.1.20; GNMT) catalyzes the AdoMet-dependent methylation of glycine to form sarcosine (N-methylglycine). Unlike most methyltransferases, GNMT is a tetrameric protein showing a positive cooperativity in AdoMet binding and weak inhibition by S-adenosylhomocysteine (AdoHcy). The first crystal structure of GNMT complexed with AdoMet showed a unique "closed" molecular basket structure, in which the N-terminal section penetrates and corks the entrance of the adjacent subunit. Thus, the apparent entrance or exit of the active site is not recognizable in the subunit structure, suggesting that the enzyme must possess a second, enzymatically active, "open" structural conformation. A new crystalline form of the R175K enzyme has been grown in the presence of an excess of AdoHcy, and its crystal structure has been determined at 3.0 A resolution. In this structure, the N-terminal domain (40 amino acid residues) of each subunit has moved out of the active site of the adjacent subunit, and the entrances of the active sites are now opened widely. An AdoHcy molecule has entered the site occupied in the "closed" structure by Glu15 and Gly16 of the N-terminal domain of the adjacent subunit. An AdoHcy binds to the consensus AdoMet binding site observed in the other methyltransferase. This AdoHcy binding site supports the glycine binding site (Arg175) deduced from a chemical modification study and site-directed mutagenesis (R175K). The crystal structures of WT and R175K enzymes were also determined at 2.5 A resolution. These enzyme structures have a closed molecular basket structure and are isomorphous to the previously determined AdoMet-GNMT structure. By comparing the open structure to the closed structure, mechanisms for auto-inhibition and for the forced release of the product AdoHcy have been revealed in the GNMT structure. The N-terminal section of the adjacent subunit occupies the AdoMet binding site and thus inhibits the methyltransfer reaction, whereas the same N-terminal section forces the departure of the potentially potent inhibitor AdoHcy from the active site and thus facilitates the methyltransfer reaction. Consequently GNMT is less active at a low level of AdoMet concentration, and is only weakly inhibited by AdoHcy. These properties of GNMT are particularly suited for regulation of the cellular AdoMet/AdoHcy ratio.
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==About this Structure== | + | </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=1d2c ConSurf]. |
| - | 1D2C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D2C OCA].
| + | <div style="clear:both"></div> |
| - | | + | __TOC__ |
| - | ==Reference== | + | </StructureSection> |
| - | Mechanisms for auto-inhibition and forced product release in glycine N-methyltransferase: crystal structures of wild-type, mutant R175K and S-adenosylhomocysteine-bound R175K enzymes., Huang Y, Komoto J, Konishi K, Takata Y, Ogawa H, Gomi T, Fujioka M, Takusagawa F, J Mol Biol. 2000 Apr 21;298(1):149-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10756111 10756111]
| + | [[Category: Large Structures]] |
| - | [[Category: Glycine N-methyltransferase]] | + | |
| | [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
| - | [[Category: Single protein]]
| + | [[Category: Huang Y]] |
| - | [[Category: Huang, Y.]] | + | [[Category: Takusagawa F]] |
| - | [[Category: Takusagawa, F.]] | + | |
| - | [[Category: methyltransferase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:33:10 2008''
| + | |
