MFTC_MYCS2
ID MFTC_MYCS2 Reviewed; 392 AA.
AC A0QSB8;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Mycofactocin maturase MftC;
DE AltName: Full=[Mycofactocin precursor peptide]-pyrrolidinone derivative synthase;
DE EC=4.1.99.26 {ECO:0000250|UniProtKB:A0PM49};
DE AltName: Full=[Mycofactocin precursor peptide]-tyrosine decarboxylase;
DE EC=1.3.98.7 {ECO:0000269|PubMed:27158836};
GN Name=mftC {ECO:0000303|PubMed:27158836};
GN OrderedLocusNames=MSMEG_1423 {ECO:0000312|EMBL:ABK73068.1};
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, CATALYTIC ACTIVITY, COFACTOR, AND REACTION MECHANISM.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=27158836; DOI=10.1021/acs.biochem.6b00355;
RA Bruender N.A., Bandarian V.;
RT "The Radical S-Adenosyl-L-methionine Enzyme MftC Catalyzes an Oxidative
RT Decarboxylation of the C-Terminus of the MftA Peptide.";
RL Biochemistry 55:2813-2816(2016).
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 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: Radical S-adenosylmethionine (SAM) enzyme responsible for the
CC first step of the biosynthesis of the enzyme cofactor mycofactocin
CC (MFT). Catalyzes two reactions at the C-terminus of the mycofactocin
CC precursor (the MftA peptide). The first one is the oxidative
CC decarboxylation of the C-terminal L-tyrosine of MftA, forming an
CC unsaturated tyramine moiety (PubMed:27158836). The second reaction is
CC the cross-linking of the tyramine with the penultimate L-valine
CC residue, forming a five-membered lactam ring (By similarity). Its
CC activity requires the presence of the MftB chaperone (PubMed:27158836).
CC Is required for the in vivo ethanol assimilation in M.smegmatis
CC (PubMed:31113891). {ECO:0000250|UniProtKB:A0PM49,
CC ECO:0000269|PubMed:27158836, ECO:0000269|PubMed:31113891}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[mycofactocin precursor peptide]-C-terminal glycyl-L-valyl-L-
CC tyrosine + S-adenosyl-L-methionine = 5'-deoxyadenosine +
CC [mycofactocin precursor peptide]-C-terminal glycyl-N-{[2-(4-
CC hydroxyphenyl)ethenyl]-3-methylbutanamide} + CO2 + L-methionine;
CC Xref=Rhea:RHEA:65492, Rhea:RHEA-COMP:16815, Rhea:RHEA-COMP:16816,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17319, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156515, ChEBI:CHEBI:156517;
CC EC=1.3.98.7; Evidence={ECO:0000269|PubMed:27158836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[mycofactocin precursor peptide]-C-terminal glycyl-N-{[2-(4-
CC hydroxyphenyl)ethenyl]-3-methylbutanamide} + AH2 + S-adenosyl-L-
CC methionine = 5'-deoxyadenosine + [mycofactocin precursor peptide]-C-
CC terminal glycyl-N-{5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-
CC oxopyrrolidin-3-yl}acetamide + A + H(+) + L-methionine;
CC Xref=Rhea:RHEA:65500, Rhea:RHEA-COMP:16816, Rhea:RHEA-COMP:16818,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15378, ChEBI:CHEBI:17319,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:156517, ChEBI:CHEBI:156518; EC=4.1.99.26;
CC Evidence={ECO:0000250|UniProtKB:A0PM49};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01266,
CC ECO:0000269|PubMed:27158836};
CC Note=Binds 3 [4Fe-4S] clusters. One cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine (Probable). All
CC three [Fe-S] clusters are required for MftC modification of MftA (By
CC similarity). {ECO:0000250|UniProtKB:A0PM49,
CC ECO:0000305|PubMed:27158836};
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene lose the ability to
CC utilize ethanol as the sole growth substrate (PubMed:31113891).
CC Glycosylated mycofactocins are not detected in this mutant
CC (PubMed:33014324). {ECO:0000269|PubMed:31113891,
CC ECO:0000269|PubMed:33014324}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. MftC family.
CC {ECO:0000305}.
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DR EMBL; CP000480; ABK73068.1; -; Genomic_DNA.
DR RefSeq; WP_011727659.1; NZ_SIJM01000016.1.
DR RefSeq; YP_885806.1; NC_008596.1.
DR AlphaFoldDB; A0QSB8; -.
DR SMR; A0QSB8; -.
DR STRING; 246196.MSMEI_1388; -.
DR EnsemblBacteria; ABK73068; ABK73068; MSMEG_1423.
DR GeneID; 66732882; -.
DR KEGG; msm:MSMEG_1423; -.
DR PATRIC; fig|246196.19.peg.1410; -.
DR eggNOG; COG0535; Bacteria.
DR OMA; GWGRQFF; -.
DR OrthoDB; 1172757at2; -.
DR BRENDA; 1.3.98.7; 3512.
DR BRENDA; 4.1.99.26; 3512.
DR Proteomes; UP000000757; Chromosome.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR023885; 4Fe4S-binding_SPASM_dom.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR023913; MftC.
DR InterPro; IPR017200; PqqE-like.
DR InterPro; IPR007197; rSAM.
DR Pfam; PF04055; Radical_SAM; 1.
DR Pfam; PF13186; SPASM; 1.
DR PIRSF; PIRSF037420; PQQ_syn_pqqE; 1.
DR SFLD; SFLDF00316; C-terminal_tyrosine_decarboxyl; 1.
DR SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR03962; mycofact_rSAM; 1.
DR TIGRFAMs; TIGR04085; rSAM_more_4Fe4S; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Iron; Iron-sulfur; Lyase; Metal-binding; Oxidoreductase;
KW Reference proteome; S-adenosyl-L-methionine.
FT CHAIN 1..392
FT /note="Mycofactocin maturase MftC"
FT /id="PRO_0000452060"
FT DOMAIN 18..228
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 354..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 32
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 36
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 39
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 253
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 260
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 271
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 312
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 315
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 321
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 325
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
FT BINDING 343
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:A0PM49"
SQ SEQUENCE 392 AA; 42378 MW; B1C3F7BAB8B5E80A CRC64;
MTSVQPVPRL VEQFERGLDA PICLTWELTY ACNLACVHCL SSSGKRDPRE LSTQQCKDII
DELERMQVFY VNIGGGEPTV RSDFWELVDY ATAHHVGVKF STNGVRITPE VAAKLAASDY
VDVQISLDGA NAEVNDAVRG KGSFDMAVRA LENLSNAGFT DAKISVVVTR QNVDQLDEFA
ALAARYGATL RITRLRPSGR GADVWDDLHP TAEQQRQLYD WLVAKGDRVL TGDSFFHLSG
LGAPGALAGL NLCGAGRVVC LIDPVGDVYA CPFAIHDKFL AGNILSDGGF QNVWQHSELF
RELREPQSAG ACASCGHFDA CRGGCMAAKF FTGLPLDGPD PECVEGWGAP ALEKERVKPK
PSGDHSRGTK QGPVALKLLT KPPARFCNES PV
