1pj5: Difference between revisions
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< | ==Crystal structure of dimethylglycine oxidase of Arthrobacter globiformis in complex with acetate== | ||
<StructureSection load='1pj5' size='340' side='right'caption='[[1pj5]], [[Resolution|resolution]] 1.61Å' scene=''> | |||
You may | == Structural highlights == | ||
<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='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='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='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> | |||
== 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 == | |||
[[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/pj/1pj5_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1pj5 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:12912903</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1pj5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Arthrobacter globiformis]] | [[Category: Arthrobacter globiformis]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Basran J]] | |||
[[Category: Basran | [[Category: Leys D]] | ||
[[Category: Leys | [[Category: Scrutton NS]] | ||
[[Category: Scrutton | |||
Latest revision as of 07:48, 17 October 2024
Crystal structure of dimethylglycine oxidase of Arthrobacter globiformis in complex with acetateCrystal structure of dimethylglycine oxidase of Arthrobacter globiformis in complex with acetate
Structural highlights
FunctionDMGO_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 PubMedHere 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
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