MGM_EUBBA
ID MGM_EUBBA Reviewed; 614 AA.
AC Q59268; Q0QLE7;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=2-methyleneglutarate mutase;
DE EC=5.4.99.4;
DE AltName: Full=Alpha-methyleneglutarate mutase;
GN Name=mgm;
OS Eubacterium barkeri (Clostridium barkeri).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Eubacteriaceae;
OC Eubacterium.
OX NCBI_TaxID=1528;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-21; 68-78; 79-103;
RP 122-126; 141-145; 395-409; 494-507; 547-552 AND 564-576, CATALYTIC
RP ACTIVITY, AND COFACTOR.
RC STRAIN=ATCC 25849 / DSM 1223 / JCM 1389 / NCIMB 10623 / VKM B-1775 / VPI
RC 5359;
RX PubMed=8168499; DOI=10.1111/j.1432-1033.1994.tb18718.x;
RA Beatrix B., Zelder O., Linder D., Buckel W.;
RT "Cloning, sequencing and expression of the gene encoding the coenzyme B12-
RT dependent 2-methyleneglutarate mutase from Clostridium barkeri in
RT Escherichia coli.";
RL Eur. J. Biochem. 221:101-109(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RC STRAIN=ATCC 25849 / DSM 1223 / JCM 1389 / NCIMB 10623 / VKM B-1775 / VPI
RC 5359;
RX PubMed=16894175; DOI=10.1073/pnas.0601635103;
RA Alhapel A., Darley D.J., Wagener N., Eckel E., Elsner N., Pierik A.J.;
RT "Molecular and functional analysis of nicotinate catabolism in Eubacterium
RT barkeri.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:12341-12346(2006).
RN [3]
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND INDUCTION.
RX PubMed=5574401; DOI=10.1016/s0021-9258(18)62235-5;
RA Kung H.F., Stadtman T.C.;
RT "Nicotinic acid metabolism. VI. Purification and properties of alpha-
RT methyleneglutarate mutase (B 12-dependent) and methylitaconate isomerase.";
RL J. Biol. Chem. 246:3378-3388(1971).
RN [4]
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=2776761; DOI=10.1111/j.1432-1033.1989.tb14995.x;
RA Michel C., Hartrampf G., Buckel W.;
RT "Assay and purification of the adenosylcobalamin-dependent 2-
RT methyleneglutarate mutase from Clostridium barkeri.";
RL Eur. J. Biochem. 184:103-107(1989).
RN [5]
RP COFACTOR.
RX PubMed=1315277; DOI=10.1111/j.1432-1033.1992.tb16841.x;
RA Michel C., Albracht S.P., Buckel W.;
RT "Adenosylcobalamin and cob(II)alamin as prosthetic groups of 2-
RT methyleneglutarate mutase from Clostridium barkeri.";
RL Eur. J. Biochem. 205:767-773(1992).
RN [6]
RP COFACTOR.
RX PubMed=8382495; DOI=10.1515/bchm3.1993.374.1-6.85;
RA Zelder O., Buckel W.;
RT "On the role of two different cobalt(II) species in coenzyme B12-dependent
RT 2-methyleneglutarate mutase from Clostridium barkeri.";
RL Biol. Chem. Hoppe-Seyler 374:85-90(1993).
RN [7]
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP HIS-464; ASP-483 AND HIS-485.
RX PubMed=16060663; DOI=10.1021/bi050049n;
RA Pierik A.J., Ciceri D., Lopez R.F., Kroll F., Broker G., Beatrix B.,
RA Buckel W., Golding B.T.;
RT "Searching for intermediates in the carbon skeleton rearrangement of 2-
RT methyleneglutarate to (R)-3-methylitaconate catalyzed by coenzyme B12-
RT dependent 2-methyleneglutarate mutase from Eubacterium barkeri.";
RL Biochemistry 44:10541-10551(2005).
CC -!- FUNCTION: Involved in the fermentation of nicotinate to ammonia,
CC propionate, acetate and carbon dioxide.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methyleneglutarate = 2-methylene-3-methylsuccinate;
CC Xref=Rhea:RHEA:13793, ChEBI:CHEBI:57637, ChEBI:CHEBI:58056;
CC EC=5.4.99.4; Evidence={ECO:0000269|PubMed:16060663,
CC ECO:0000269|PubMed:2776761, ECO:0000269|PubMed:5574401,
CC ECO:0000269|PubMed:8168499};
CC -!- COFACTOR:
CC Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408;
CC Evidence={ECO:0000269|PubMed:1315277, ECO:0000269|PubMed:16060663,
CC ECO:0000269|PubMed:5574401, ECO:0000269|PubMed:8168499,
CC ECO:0000269|PubMed:8382495};
CC Name=cob(II)alamin; Xref=ChEBI:CHEBI:16304;
CC Evidence={ECO:0000269|PubMed:1315277, ECO:0000269|PubMed:16060663,
CC ECO:0000269|PubMed:5574401, ECO:0000269|PubMed:8168499,
CC ECO:0000269|PubMed:8382495};
CC Note=Contains a mixture of adenosylcobalamin and oxygen-stable
CC cob(II)alamin. {ECO:0000269|PubMed:1315277,
CC ECO:0000269|PubMed:16060663, ECO:0000269|PubMed:5574401,
CC ECO:0000269|PubMed:8168499, ECO:0000269|PubMed:8382495};
CC -!- ACTIVITY REGULATION: Inhibited by intrinsic factor and iodoacetic acid.
CC Competitively inhibited by itaconate, mesaconate, succinate, 1-methyl-
CC 1,2-trans-clycopropane, dicarboxylate and L-malate. Non-competitively
CC inhibited by glutaconate and 1-methyl-1,2-cis-
CC cyclopropanedicarboxylate. Not inhibited by acrylate or by the
CC chelating agents alpha,alpha-dipyridyl or EDTA. Not activated by
CC Fe(2+), Mg(2+), Mn(2+) or Ca(2+). Unaffected by K(+), Na(+), NH4(+),
CC Rb(+) or Li(+). {ECO:0000269|PubMed:16060663,
CC ECO:0000269|PubMed:5574401}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Activity decreases rapidly below pH 7.5 in phosphate buffer, and
CC below pH 8.0 in Tris buffer. {ECO:0000269|PubMed:5574401};
CC -!- PATHWAY: Cofactor degradation; nicotinate degradation; propanoate and
CC pyruvate from 6-hydroxynicotinate: step 5/8.
CC {ECO:0000269|PubMed:16894175}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:2776761}.
CC -!- INDUCTION: By nicotinate. {ECO:0000269|PubMed:5574401}.
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DR EMBL; X77484; CAA54625.1; -; Genomic_DNA.
DR EMBL; DQ310789; ABC88403.1; -; Genomic_DNA.
DR PIR; S43237; S43237.
DR AlphaFoldDB; Q59268; -.
DR SMR; Q59268; -.
DR STRING; 1528.SAMN04488579_1129; -.
DR KEGG; ag:CAA54625; -.
DR BioCyc; MetaCyc:MON-11712; -.
DR UniPathway; UPA01010; UER01016.
DR GO; GO:0047548; F:2-methyleneglutarate mutase activity; IDA:UniProtKB.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1901848; P:nicotinate catabolic process; IDA:UniProtKB.
DR InterPro; IPR006159; Acid_CoA_mut_C.
DR InterPro; IPR016176; Cbl-dep_enz_cat.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR Pfam; PF02310; B12-binding; 1.
DR SUPFAM; SSF51703; SSF51703; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR TIGRFAMs; TIGR00640; acid_CoA_mut_C; 1.
DR PROSITE; PS51332; B12_BINDING; 1.
PE 1: Evidence at protein level;
KW Cobalamin; Cobalt; Direct protein sequencing; Isomerase; Metal-binding.
FT CHAIN 1..614
FT /note="2-methyleneglutarate mutase"
FT /id="PRO_0000096464"
FT DOMAIN 472..614
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT BINDING 485
FT /ligand="adenosylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:18408"
FT /ligand_part="Co"
FT /ligand_part_id="ChEBI:CHEBI:27638"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
FT MUTAGEN 464
FT /note="H->Q: No effect on activity."
FT /evidence="ECO:0000269|PubMed:16060663"
FT MUTAGEN 483
FT /note="D->N: Activity reduced 2000-fold."
FT /evidence="ECO:0000269|PubMed:16060663"
FT MUTAGEN 485
FT /note="H->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16060663"
FT CONFLICT 97
FT /note="K -> W (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 614 AA; 66750 MW; 37B78FEB06A4A3D1 CRC64;
MQEKTKRIIK EDIEAVRAYS DCFDVEMPDL DENGEVIGLP APYPREVAGT VRSGYRIYDL
AKKAKERGWP IQNPILGRNT AEETYGESQE MYAYADKFDE TLFHFVHAEA TRHIDPLKGR
ELINQSRGKG GITPIGEREF IAMGGGSKHP VRINATGDTP HLSIINALIA GFDGTDIGPV
IHVHFGGRGI HDYKTKVVNG YKAIQICAEN NIFVQLDSHK HLNNIGGTDG MALAMCLLSE
GLAVHAGLPW ELSAIQMNVA GINIYADLAV MRAFRKACHS KSIIAVPETF QNPPGNLVAE
AAHFSRMAVT AKLGGADFYR PKAAESVGIP TGDSMGQAIW GTEDVFGHVV NPDIQSPVID
AREAEIIDEA LAVLEATLHL EGLTLEAMTD DFWKQWSDEA LIDLIVAAGK AGVLDSQRAA
GWDLKRHVVV NRDKDGITRY VKGYTPLGVD ASRCAQSDED VEVHVEKAPT RPEKIVLATV
GADAHVNGIN VIREAFQDAG YDVVYLRGMN LPESVAEVAA EVGADAVGVS NLLGLGMELF
PRVSKRLEEL GLRDKMVVCA GGRIAEKEEE HRQFEEKIQK EGSAFMGMDG FFGPGSSPED
CVKIIGDMIN AKKA
