MFTC_MYCUA
ID MFTC_MYCUA Reviewed; 369 AA.
AC A0PM49;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Mycofactocin maturase MftC {ECO:0000303|PubMed:30628436};
DE AltName: Full=[Mycofactocin precursor peptide]-pyrrolidinone derivative synthase {ECO:0000305|PubMed:28634235};
DE EC=4.1.99.26 {ECO:0000269|PubMed:28634235};
DE AltName: Full=[Mycofactocin precursor peptide]-tyrosine decarboxylase;
DE EC=1.3.98.7 {ECO:0000269|PubMed:27312813, ECO:0000269|PubMed:28634235};
GN Name=mftC {ECO:0000303|PubMed:27312813, ECO:0000303|PubMed:28634235};
GN OrderedLocusNames=MUL_0773 {ECO:0000312|EMBL:ABL03418.1};
OS Mycobacterium ulcerans (strain Agy99).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=362242;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Agy99;
RX PubMed=17210928; DOI=10.1101/gr.5942807;
RA Stinear T.P., Seemann T., Pidot S., Frigui W., Reysset G., Garnier T.,
RA Meurice G., Simon D., Bouchier C., Ma L., Tichit M., Porter J.L., Ryan J.,
RA Johnson P.D.R., Davies J.K., Jenkin G.A., Small P.L.C., Jones L.M.,
RA Tekaia F., Laval F., Daffe M., Parkhill J., Cole S.T.;
RT "Reductive evolution and niche adaptation inferred from the genome of
RT Mycobacterium ulcerans, the causative agent of Buruli ulcer.";
RL Genome Res. 17:192-200(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND INTERACTION WITH MFTB.
RX PubMed=27312813; DOI=10.1002/1873-3468.12249;
RA Khaliullin B., Aggarwal P., Bubas M., Eaton G.R., Eaton S.S., Latham J.A.;
RT "Mycofactocin biosynthesis: modification of the peptide MftA by the radical
RT S-adenosylmethionine protein MftC.";
RL FEBS Lett. 590:2538-2548(2016).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND REACTION MECHANISM.
RC STRAIN=Agy99;
RX PubMed=28634235; DOI=10.1074/jbc.m117.795682;
RA Khaliullin B., Ayikpoe R., Tuttle M., Latham J.A.;
RT "Mechanistic elucidation of the mycofactocin-biosynthetic radical S-
RT adenosylmethionine protein, MftC.";
RL J. Biol. Chem. 292:13022-13033(2017).
RN [4]
RP COFACTOR, MOSSBAUER SPECTROSCOPY, AND IRON-SULFUR CLUSTER BINDING SITES.
RC STRAIN=Agy99;
RX PubMed=30628436; DOI=10.1021/acs.biochem.8b01082;
RA Ayikpoe R., Ngendahimana T., Langton M., Bonitatibus S., Walker L.M.,
RA Eaton S.S., Eaton G.R., Pandelia M.E., Elliott S.J., Latham J.A.;
RT "Spectroscopic and Electrochemical Characterization of the Mycofactocin
RT Biosynthetic Protein, MftC, Provides Insight into Its Redox Flipping
RT Mechanism.";
RL Biochemistry 58:940-950(2019).
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:27312813, PubMed:28634235). The
CC second reaction is the cross-linking of the tyramine with the
CC penultimate L-valine residue, forming a five-membered lactam ring
CC (PubMed:28634235). Its activity requires the presence of the MftB
CC chaperone (PubMed:27312813). {ECO:0000269|PubMed:27312813,
CC ECO:0000269|PubMed:28634235}.
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:27312813,
CC ECO:0000269|PubMed:28634235};
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:0000269|PubMed:28634235};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:27312813, ECO:0000269|PubMed:30628436};
CC Note=Binds 3 [4Fe-4S] clusters. One cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine. All three [Fe-S]
CC clusters are required for MftC modification of MftA.
CC {ECO:0000269|PubMed:30628436};
CC -!- SUBUNIT: Interacts with MftB. {ECO:0000269|PubMed:27312813}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. MftC family.
CC {ECO:0000305}.
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DR EMBL; CP000325; ABL03418.1; -; Genomic_DNA.
DR AlphaFoldDB; A0PM49; -.
DR SMR; A0PM49; -.
DR STRING; 362242.MUL_0773; -.
DR EnsemblBacteria; ABL03418; ABL03418; MUL_0773.
DR KEGG; mul:MUL_0773; -.
DR eggNOG; COG0535; Bacteria.
DR HOGENOM; CLU_009273_4_3_11; -.
DR OMA; GWGRQFF; -.
DR BioCyc; MetaCyc:MON-21112; -.
DR BRENDA; 1.3.8.17; 8016.
DR BRENDA; 1.3.98.7; 8016.
DR BRENDA; 4.1.99.26; 8016.
DR Proteomes; UP000000765; 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 S-adenosyl-L-methionine.
FT CHAIN 1..369
FT /note="Mycofactocin maturase MftC"
FT /id="PRO_0000452061"
FT DOMAIN 16..232
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 347..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 355..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 30
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:0000255|PROSITE-ProRule:PRU01266,
FT ECO:0000305|PubMed:30628436"
FT BINDING 34
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:0000255|PROSITE-ProRule:PRU01266,
FT ECO:0000305|PubMed:30628436"
FT BINDING 37
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:0000255|PROSITE-ProRule:PRU01266,
FT ECO:0000305|PubMed:30628436"
FT BINDING 251
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 258
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 269
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 310
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 313
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 319
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 323
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:30628436"
FT BINDING 341
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:30628436"
SQ SEQUENCE 369 AA; 39558 MW; A8A53D305D050AAA CRC64;
MTTAVPRLIE QFEHGLDAPI CLTWELTYAC NLACVHCLSS SGKRDPGELS TRQCQDIIDE
LERMQVFYVN IGGGEPTVRP DFWELVDYAT AHHVGVKFST NGVRINPEVA ARLAASDCVD
VQISLDGATA EVNDAVRGAG SFAMAVRALE NLAAAGFADA KISVVVTRHN VGQLDDFAAL
ADRYGATLRI TRLRPSGRGA DVWEELHPTA AQQVALYDWL VAKGERVLTG DSFFHLAPLG
SSGALAGLNM CGAGRVVCLI DPVGDVYACP FAIHDRFLAG NVLTDGGFDQ VWKNAPLFRQ
LREPQSAGAC GSCGHYDSCR GGCMAAKFFT GLPLDGPDPE CVQGYGAPAL AQERHAPRPR
VDHSRGSRE
