MFTD_MYCS2
ID MFTD_MYCS2 Reviewed; 399 AA.
AC A0QSB9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Pre-mycofactocin synthase {ECO:0000305|PubMed:31381312};
DE Short=PMFT synthase {ECO:0000305|PubMed:31381312};
DE EC=1.4.3.26 {ECO:0000269|PubMed:31381312};
GN Name=mftD {ECO:0000303|PubMed:31381312};
GN OrderedLocusNames=MSMEG_1424 {ECO:0000312|EMBL:ABK72067.1};
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=31381312; DOI=10.1021/jacs.9b06102;
RA Ayikpoe R.S., Latham J.A.;
RT "MftD Catalyzes the Formation of a Biologically Active Redox Center in the
RT Biosynthesis of the Ribosomally Synthesized and Post-translationally
RT Modified Redox Cofactor Mycofactocin.";
RL J. Am. Chem. Soc. 141:13582-13591(2019).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=31113891; DOI=10.1128/mbio.00190-19;
RA Krishnamoorthy G., Kaiser P., Lozza L., Hahnke K., Mollenkopf H.J.,
RA Kaufmann S.H.E.;
RT "Mycofactocin Is Associated with Ethanol Metabolism in Mycobacteria.";
RL MBio 10:E00190-E00190(2019).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=33014324; DOI=10.1039/d0sc01172j;
RA Pena-Ortiz L., Graca A.P., Guo H., Braga D., Koellner T.G., Regestein L.,
RA Beemelmanns C., Lackner G.;
RT "Structure elucidation of the redox cofactor mycofactocin reveals oligo-
RT glycosylation by MftF.";
RL Chem. Sci. 11:5182-5190(2020).
CC -!- FUNCTION: Involved in the biosynthesis of the enzyme cofactor
CC mycofactocin (MFT) (PubMed:33014324). Catalyzes the oxidative
CC deamination of AHDP (3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-
CC 2-pyrrolidin-2-one), forming an alpha-keto amide moiety on the
CC resulting molecule, which is called pre-mycofactocin (PMFT). This
CC reaction occurs via a 5-[(4-hydroxyphenyl)methyl]-3-imino-4,4-
CC dimethylpyrrolidin-2-one intermediate, which converts to PMFT. The
CC alpha-keto amide moiety is the redox-active center for the redox
CC activity of mycofactocin (PubMed:31381312). Is required for the in vivo
CC ethanol assimilation in M.smegmatis (PubMed:31113891).
CC {ECO:0000269|PubMed:31113891, ECO:0000269|PubMed:31381312,
CC ECO:0000269|PubMed:33014324}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-
CC 2-one + H2O + O2 = H2O2 + NH4(+) + pre-mycofactocin;
CC Xref=Rhea:RHEA:65508, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:150862,
CC ChEBI:CHEBI:150863; EC=1.4.3.26;
CC Evidence={ECO:0000269|PubMed:31381312};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:A0PM50};
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene lose the ability to
CC utilize ethanol as the sole growth substrate (PubMed:31113891). They
CC are unable to produce PMFT(H2) and glycosylated (methyl)MFT(H2), and
CC accumulate AHDP and glycosylated AHDP (PubMed:33014324).
CC {ECO:0000269|PubMed:31113891, ECO:0000269|PubMed:33014324}.
CC -!- SIMILARITY: Belongs to the FMN-dependent alpha-hydroxy acid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; CP000480; ABK72067.1; -; Genomic_DNA.
DR RefSeq; YP_885807.1; NC_008596.1.
DR AlphaFoldDB; A0QSB9; -.
DR SMR; A0QSB9; -.
DR STRING; 246196.MSMEI_1389; -.
DR PRIDE; A0QSB9; -.
DR EnsemblBacteria; ABK72067; ABK72067; MSMEG_1424.
DR KEGG; msm:MSMEG_1424; -.
DR PATRIC; fig|246196.19.peg.1411; -.
DR eggNOG; COG1304; Bacteria.
DR OMA; AWSWEKI; -.
DR BRENDA; 1.4.3.26; 3512.
DR Proteomes; UP000000757; Chromosome.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR CDD; cd02809; alpha_hydroxyacid_oxid_FMN; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR012133; Alpha-hydoxy_acid_DH_FMN.
DR InterPro; IPR000262; FMN-dep_DH.
DR InterPro; IPR037396; FMN_HAD.
DR InterPro; IPR023989; MftD.
DR Pfam; PF01070; FMN_dh; 1.
DR PIRSF; PIRSF000138; Al-hdrx_acd_dh; 1.
DR TIGRFAMs; TIGR03966; actino_HemFlav; 1.
DR PROSITE; PS51349; FMN_HYDROXY_ACID_DH_2; 1.
PE 1: Evidence at protein level;
KW Flavoprotein; FMN; Oxidoreductase; Reference proteome.
FT CHAIN 1..399
FT /note="Pre-mycofactocin synthase"
FT /id="PRO_0000452053"
FT DOMAIN 4..386
FT /note="FMN hydroxy acid dehydrogenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT ACT_SITE 281
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 111
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 131
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 133
FT /ligand="a 2-oxocarboxylate"
FT /ligand_id="ChEBI:CHEBI:35179"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 159
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 168
FT /ligand="a 2-oxocarboxylate"
FT /ligand_id="ChEBI:CHEBI:35179"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 257
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 312..316
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 335..336
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
SQ SEQUENCE 399 AA; 42774 MW; 68E90B93376382AE CRC64;
MNMARDIWFE TVAIAQQRAR KRLPKSVYSS LISASEKGVT VTDNVESFAE LGFAPHVVGA
PEKRDMATTV MGQQISLPVI ISPTGVQAVH PDGEVAVARA AAARGTAMGL SSFASKPIEE
VVAVNDKIFF QIYWLGDRDA ILARAERAKA AGAVGLIVTT DWSFSHGRDW GSPKIPEKMD
LKTMVTMMPE ALTKPRWLWQ WGKTMRPPNL RVPNQGARGE DGPPFFQAYG EWMGTPPPTW
EDIAWLREQW DGPFMLKGVI RVDDAKRAVD AGVSAISVSN HGGNNLDGTP AAIRALPVIA
EAVGDQVEVL LDGGIRRGSD VVKAVALGAR AVMIGRAYLW GLAAEGQVGV ENVLDILRGG
IDSALMGLGR SSIHDLVPED ILVPEGFTRA LGVPPASGS
