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| | <StructureSection load='1pj5' size='340' side='right'caption='[[1pj5]], [[Resolution|resolution]] 1.61Å' scene=''> | | <StructureSection load='1pj5' size='340' side='right'caption='[[1pj5]], [[Resolution|resolution]] 1.61Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1pj5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"achromobacter_globiformis"_(conn_1928)_bergey_et_al._1930 "achromobacter globiformis" (conn 1928) bergey et al. 1930]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PJ5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1pj5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PJ5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.61Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pj6|1pj6]], [[1pj7|1pj7]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dimethylglycine_oxidase Dimethylglycine oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.10 1.5.3.10] </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=1pj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pj5 OCA], [https://pdbe.org/1pj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pj5 RCSB], [https://www.ebi.ac.uk/pdbsum/1pj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pj5 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=1pj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pj5 OCA], [https://pdbe.org/1pj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pj5 RCSB], [https://www.ebi.ac.uk/pdbsum/1pj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pj5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DMGO_ARTGO DMGO_ARTGO] Catalyzes the oxidative demethylation of N,N-dimethylglycine to yield sarcosine, formaldehyde and hydrogen peroxide. The oxidation of dimethylglycine is coupled to the synthesis of 5,10-methylenetetrahydrofolate through an unusual substrate channeling mechanism. This channeling occurs by nonbiased diffusion of the iminium intermediate through a large solvent cavity connecting active site 1 (N-terminus) and active site 2 (C-terminus). The synthesis of 5,10-methylenetetrahydrofolate (at active site 2) prevents the accumulation of formaldehyde, formed by hydrolysis of the iminium intermediate product (at active site 1). Does not oxidize sarcosine.<ref>PMID:11422368</ref> <ref>PMID:11926836</ref> <ref>PMID:12912903</ref> <ref>PMID:19369258</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pj/1pj5_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pj/1pj5_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dimethylglycine oxidase]] | + | [[Category: Arthrobacter globiformis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Basran, J]] | + | [[Category: Basran J]] |
| - | [[Category: Leys, D]] | + | [[Category: Leys D]] |
| - | [[Category: Scrutton, N S]] | + | [[Category: Scrutton NS]] |
| - | [[Category: Amine oxidase]]
| + | |
| - | [[Category: Channelling]]
| + | |
| - | [[Category: Fad binding]]
| + | |
| - | [[Category: Folate binding]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DMGO_ARTGO Catalyzes the oxidative demethylation of N,N-dimethylglycine to yield sarcosine, formaldehyde and hydrogen peroxide. The oxidation of dimethylglycine is coupled to the synthesis of 5,10-methylenetetrahydrofolate through an unusual substrate channeling mechanism. This channeling occurs by nonbiased diffusion of the iminium intermediate through a large solvent cavity connecting active site 1 (N-terminus) and active site 2 (C-terminus). The synthesis of 5,10-methylenetetrahydrofolate (at active site 2) prevents the accumulation of formaldehyde, formed by hydrolysis of the iminium intermediate product (at active site 1). Does not oxidize sarcosine.[1] [2] [3] [4]
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
Here we report crystal structures of dimethylglycine oxidase (DMGO) from the bacterium Arthrobacter globiformis, a bifunctional enzyme that catalyzes the oxidation of N,N-dimethyl glycine and the formation of 5,10-methylene tetrahydrofolate. The N-terminal region binds FAD covalently and oxidizes dimethylglycine to a labile iminium intermediate. The C-terminal region binds tetrahydrofolate, comprises three domains arranged in a ring-like structure and is related to the T-protein of the glycine cleavage system. The complex with folinic acid indicates that this enzyme selectively activates the N10 amino group for initial attack on the substrate. Dead-end reactions with oxidized folate are avoided by the strict stereochemical constraints imposed by the folate-binding funnel. The active sites in DMGO are approximately 40 A apart, connected by a large irregular internal cavity. The tetrahydrofolate-binding funnel serves as a transient entry-exit port, and access to the internal cavity is controlled kinetically by tetrahydrofolate binding. The internal cavity enables sequestration of the reactive iminium intermediate prior to reaction with tetrahydrofolate and avoids formation of toxic formaldehyde. This mode of channelling in DMGO is distinct from other channelling mechanisms.
Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase.,Leys D, Basran J, Scrutton NS EMBO J. 2003 Aug 15;22(16):4038-48. PMID:12912903[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meskys R, Harris RJ, Casaite V, Basran J, Scrutton NS. Organization of the genes involved in dimethylglycine and sarcosine degradation in Arthrobacter spp.: implications for glycine betaine catabolism. Eur J Biochem. 2001 Jun;268(12):3390-8. PMID:11422368 doi:10.1046/j.1432-1327.2001.02239.x
- ↑ Basran J, Bhanji N, Basran A, Nietlispach D, Mistry S, Meskys R, Scrutton NS. Mechanistic aspects of the covalent flavoprotein dimethylglycine oxidase of Arthrobacter globiformis studied by stopped-flow spectrophotometry. Biochemistry. 2002 Apr 9;41(14):4733-43. PMID:11926836 doi:10.1021/bi025519h
- ↑ Leys D, Basran J, Scrutton NS. Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase. EMBO J. 2003 Aug 15;22(16):4038-48. PMID:12912903 doi:http://dx.doi.org/10.1093/emboj/cdg395
- ↑ Tralau T, Lafite P, Levy C, Combe JP, Scrutton NS, Leys D. An internal reaction chamber in dimethylglycine oxidase provides efficient protection from exposure to toxic formaldehyde. J Biol Chem. 2009 Jun 26;284(26):17826-34. Epub 2009 Apr 15. PMID:19369258 doi:10.1074/jbc.M109.006262
- ↑ Leys D, Basran J, Scrutton NS. Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase. EMBO J. 2003 Aug 15;22(16):4038-48. PMID:12912903 doi:http://dx.doi.org/10.1093/emboj/cdg395
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