DMGO_ARTGO
ID DMGO_ARTGO Reviewed; 830 AA.
AC Q9AGP8;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Dimethylglycine oxidase;
DE Short=DMGO;
DE EC=1.5.3.10;
GN Name=dmg;
OS Arthrobacter globiformis.
OC Bacteria; Actinobacteria; Micrococcales; Micrococcaceae; Arthrobacter.
OX NCBI_TaxID=1665;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=NRRL B-2979;
RX PubMed=11422368; DOI=10.1046/j.1432-1327.2001.02239.x;
RA Meskys R., Harris R.J., Casaite V., Basran J., Scrutton N.S.;
RT "Organization of the genes involved in dimethylglycine and sarcosine
RT degradation in Arthrobacter spp.: implications for glycine betaine
RT catabolism.";
RL Eur. J. Biochem. 268:3390-3398(2001).
RN [2]
RP PROTEIN SEQUENCE OF 27-58, FUNCTION, AND FAD-BINDING AT HIS-48.
RC STRAIN=NRRL B-2979;
RX PubMed=11926836; DOI=10.1021/bi025519h;
RA Basran J., Bhanji N., Basran A., Nietlispach D., Mistry S., Meskys R.,
RA Scrutton N.S.;
RT "Mechanistic aspects of the covalent flavoprotein dimethylglycine oxidase
RT of Arthrobacter globiformis studied by stopped-flow spectrophotometry.";
RL Biochemistry 41:4733-4743(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.61 ANGSTROMS) IN COMPLEX WITH FAD AND
RP TETRAHYDROFOLATE, FUNCTION, AND MUTAGENESIS OF HIS-225 AND TYR-259.
RC STRAIN=NRRL B-2979;
RX PubMed=12912903; DOI=10.1093/emboj/cdg395;
RA Leys D., Basran J., Scrutton N.S.;
RT "Channelling and formation of 'active' formaldehyde in dimethylglycine
RT oxidase.";
RL EMBO J. 22:4038-4048(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 4-830 IN COMPLEX WITH FAD AND
RP TETRAHYDROFOLATE, FUNCTION, AND MUTAGENESIS OF ASP-552.
RC STRAIN=NRRL B-2979;
RX PubMed=19369258; DOI=10.1074/jbc.m109.006262;
RA Tralau T., Lafite P., Levy C., Combe J.P., Scrutton N.S., Leys D.;
RT "An internal reaction chamber in dimethylglycine oxidase provides efficient
RT protection from exposure to toxic formaldehyde.";
RL J. Biol. Chem. 284:17826-17834(2009).
CC -!- FUNCTION: Catalyzes the oxidative demethylation of N,N-dimethylglycine
CC to yield sarcosine, formaldehyde and hydrogen peroxide. The oxidation
CC of dimethylglycine is coupled to the synthesis of 5,10-
CC methylenetetrahydrofolate through an unusual substrate channeling
CC mechanism. This channeling occurs by nonbiased diffusion of the iminium
CC intermediate through a large solvent cavity connecting active site 1
CC (N-terminus) and active site 2 (C-terminus). The synthesis of 5,10-
CC methylenetetrahydrofolate (at active site 2) prevents the accumulation
CC of formaldehyde, formed by hydrolysis of the iminium intermediate
CC product (at active site 1). Does not oxidize sarcosine.
CC {ECO:0000269|PubMed:11422368, ECO:0000269|PubMed:11926836,
CC ECO:0000269|PubMed:12912903, ECO:0000269|PubMed:19369258}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,N-dimethylglycine + O2 = formaldehyde + H2O2 +
CC sarcosine; Xref=Rhea:RHEA:17077, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:57433, ChEBI:CHEBI:58251; EC=1.5.3.10;
CC Evidence={ECO:0000269|PubMed:11422368};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + N,N-dimethylglycine + O2 =
CC (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + H2O2 + sarcosine;
CC Xref=Rhea:RHEA:45756, ChEBI:CHEBI:15379, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:57433, ChEBI:CHEBI:57453,
CC ChEBI:CHEBI:58251; Evidence={ECO:0000269|PubMed:11422368};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:11422368, ECO:0000269|PubMed:11926836};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:11422368,
CC ECO:0000269|PubMed:11926836};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 mM for N,N-dimethylglycine {ECO:0000269|PubMed:11422368};
CC pH dependence:
CC Optimum pH is 8.0-10.0. {ECO:0000269|PubMed:11422368};
CC -!- SIMILARITY: Belongs to the GcvT family. {ECO:0000305}.
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DR EMBL; AF329477; AAK16482.1; -; Genomic_DNA.
DR PDB; 1PJ5; X-ray; 1.61 A; A=1-830.
DR PDB; 1PJ6; X-ray; 1.65 A; A=1-830.
DR PDB; 1PJ7; X-ray; 2.10 A; A=1-830.
DR PDB; 3GSI; X-ray; 2.00 A; A=4-830.
DR PDBsum; 1PJ5; -.
DR PDBsum; 1PJ6; -.
DR PDBsum; 1PJ7; -.
DR PDBsum; 3GSI; -.
DR AlphaFoldDB; Q9AGP8; -.
DR SMR; Q9AGP8; -.
DR DrugBank; DB03256; (6R)-Folinic acid.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR PRIDE; Q9AGP8; -.
DR KEGG; ag:AAK16482; -.
DR BioCyc; MetaCyc:MON-21836; -.
DR BRENDA; 1.5.3.10; 444.
DR SABIO-RK; Q9AGP8; -.
DR EvolutionaryTrace; Q9AGP8; -.
DR GO; GO:0047866; F:dimethylglycine oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1360.120; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR032503; FAO_M.
DR InterPro; IPR013977; GCV_T_C.
DR InterPro; IPR006222; GCV_T_N.
DR InterPro; IPR029043; GcvT/YgfZ_C.
DR InterPro; IPR027266; TrmE/GcvT_dom1.
DR Pfam; PF01266; DAO; 1.
DR Pfam; PF16350; FAO_M; 1.
DR Pfam; PF01571; GCV_T; 1.
DR Pfam; PF08669; GCV_T_C; 1.
DR SUPFAM; SSF101790; SSF101790; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; FAD; Flavoprotein;
KW Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..830
FT /note="Dimethylglycine oxidase"
FT /id="PRO_0000428956"
FT ACT_SITE 225
FT /evidence="ECO:0000255"
FT ACT_SITE 259
FT /evidence="ECO:0000255"
FT ACT_SITE 552
FT /note="For 5,10-methylenetetrahydrofolate synthesis
FT activity"
FT /evidence="ECO:0000255"
FT BINDING 14..15
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 45..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 52
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 174
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 259
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 360..363
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12912903,
FT ECO:0000269|PubMed:19369258"
FT BINDING 539
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000269|PubMed:19369258"
FT BINDING 554
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT BINDING 566
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT BINDING 658..660
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT SITE 225
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000269|PubMed:12912903"
FT SITE 259
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000269|PubMed:12912903"
FT SITE 552
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000269|PubMed:19369258,
FT ECO:0000305|PubMed:12912903"
FT MOD_RES 48
FT /note="Pros-8alpha-FAD histidine"
FT MUTAGEN 225
FT /note="H->Q: Reduces catalytic efficiency 3-fold and
FT substrate affinity 30-fold."
FT /evidence="ECO:0000269|PubMed:12912903"
FT MUTAGEN 259
FT /note="Y->F: Reduces catalytic efficiency 225-fold and
FT substrate affinity 25-fold."
FT /evidence="ECO:0000269|PubMed:12912903"
FT MUTAGEN 552
FT /note="D->A: No effect on the activity."
FT /evidence="ECO:0000269|PubMed:19369258"
FT MUTAGEN 552
FT /note="D->N: Reduces activity 3-fold."
FT /evidence="ECO:0000269|PubMed:19369258"
FT STRAND 7..10
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 14..25
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 60..75
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 96..112
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 121..127
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 150..163
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 174..180
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 183..189
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 221..231
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 305..318
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 320..324
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 327..337
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 344..347
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 362..364
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 365..378
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 395..398
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 400..412
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 436..441
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 444..449
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 452..458
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 459..467
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 479..482
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 488..498
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 501..504
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 510..515
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 518..525
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 536..543
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 549..559
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 562..566
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 570..586
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 594..597
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 599..601
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 602..609
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 612..616
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 617..619
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 626..628
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 633..639
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 642..647
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 653..662
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 663..677
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 678..680
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 683..685
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 687..696
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 702..704
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 712..716
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 718..720
FT /evidence="ECO:0007829|PDB:1PJ5"
FT HELIX 731..734
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 739..741
FT /evidence="ECO:0007829|PDB:3GSI"
FT STRAND 743..751
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 763..766
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 769..773
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 776..780
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 781..784
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 785..793
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 801..806
FT /evidence="ECO:0007829|PDB:1PJ5"
FT STRAND 809..816
FT /evidence="ECO:0007829|PDB:1PJ5"
FT TURN 826..828
FT /evidence="ECO:0007829|PDB:1PJ5"
SQ SEQUENCE 830 AA; 89985 MW; 13DE3C4B3DF325DA CRC64;
MASTPRIVII GAGIVGTNLA DELVTRGWNN ITVLDQGPLN MPGGSTSHAP GLVFQTNPSK
TMASFAKYTV EKLLSLTEDG VSCFNQVGGL EVATTETRLA DLKRKLGYAA AWGIEGRLLS
PAECQELYPL LDGENILGGL HVPSDGLASA ARAVQLLIKR TESAGVTYRG STTVTGIEQS
GGRVTGVQTA DGVIPADIVV SCAGFWGAKI GAMIGMAVPL LPLAHQYVKT TPVPAQQGRN
DQPNGARLPI LRHQDQDLYY REHGDRYGIG SYAHRPMPVD VDTLGAYAPE TVSEHHMPSR
LDFTLEDFLP AWEATKQLLP ALADSEIEDG FNGIFSFTPD GGPLLGESKE LDGFYVAEAV
WVTHSAGVAK AMAELLTTGR SETDLGECDI TRFEDVQLTP EYVSETSQQN FVEIYDVLHP
LQPRLSPRNL RVSPFHARHK ELGAFFLEAG GWERPYWFEA NAALLKEMPA EWLPPARDAW
SGMFSSPIAA AEAWKTRTAV AMYDMTPLKR LEVSGPGALK LLQELTTADL AKKPGAVTYT
LLLDHAGGVR SDITVARLSE DTFQLGANGN IDTAYFERAA RHQTQSGSAT DWVQVRDTTG
GTCCIGLWGP LARDLVSKVS DDDFTNDGLK YFRAKNVVIG GIPVTAMRLS YVGELGWELY
TSADNGQRLW DALWQAGQPF GVIAAGRAAF SSLRLEKGYR SWGTDMTTEH DPFEAGLGFA
VKMAKESFIG KGALEGRTEE ASARRLRCLT IDDGRSIVLG KEPVFYKEQA VGYVTSAAYG
YTVAKPIAYS YLPGTVSVGD SVDIEYFGRR ITATVTEDPL YDPKMTRLRG
