3gsi
From Proteopedia
(Difference between revisions)
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<StructureSection load='3gsi' size='340' side='right'caption='[[3gsi]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='3gsi' size='340' side='right'caption='[[3gsi]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3gsi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3gsi]] 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=3GSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GSI FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=THG:(6S)-5,6,7,8-TETRAHYDROFOLATE'>THG</scene></td></tr> | |
| - | <tr id=' | + | |
| - | < | + | |
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gsi OCA], [https://pdbe.org/3gsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gsi RCSB], [https://www.ebi.ac.uk/pdbsum/3gsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gsi 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=3gsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gsi OCA], [https://pdbe.org/3gsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gsi RCSB], [https://www.ebi.ac.uk/pdbsum/3gsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gsi 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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</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=3gsi ConSurf]. | </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=3gsi ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | We report a synthetic biology approach to demonstrate substrate channeling in an unusual bifunctional flavoprotein dimethylglycine oxidase. The catabolism of dimethylglycine through methyl group oxidation can potentially liberate toxic formaldehyde, a problem common to many amine oxidases and dehydrogenases. Using a novel synthetic in vivo reporter system for cellular formaldehyde, we found that the oxidation of dimethylglycine is coupled to the synthesis of 5,10-methylenetetrahydrofolate through an unusual substrate channeling mechanism. We also showed that uncoupling of the active sites could be achieved by mutagenesis or deletion of the 5,10-methylenetetrahydrofolate synthase site and that this leads to accumulation of intracellular formaldehyde. Channeling occurs by nonbiased diffusion of the labile intermediate through a large solvent cavity connecting both active sites. This central "reaction chamber" is created by a modular protein architecture that appears primitive when compared with the sophisticated design of other paradigm substrate-channeling enzymes. The evolutionary origins of the latter were likely similar to dimethylglycine oxidase. This work demonstrates the utility of synthetic biology approaches to the study of enzyme mechanisms in vivo and points to novel channeling mechanisms that protect the cell milieu from potentially toxic reaction products. | ||
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| - | An internal reaction chamber in dimethylglycine oxidase provides efficient protection from exposure to toxic formaldehyde.,Tralau T, Lafite P, Levy C, Combe JP, Scrutton NS, Leys D J Biol Chem. 2009 Jun 26;284(26):17826-34. Epub 2009 Apr 15. PMID:19369258<ref>PMID:19369258</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3gsi" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Arthrobacter globiformis]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Combe | + | [[Category: Combe JP]] |
| - | [[Category: Lafite | + | [[Category: Lafite P]] |
| - | [[Category: Levy | + | [[Category: Levy C]] |
| - | [[Category: Leys | + | [[Category: Leys D]] |
| - | [[Category: Scrutton | + | [[Category: Scrutton NS]] |
| - | [[Category: Tralau | + | [[Category: Tralau T]] |
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Current revision
Crystal structure of D552A dimethylglycine oxidase mutant of Arthrobacter globiformis in complex with tetrahydrofolate
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