MFTE_MYCS2
ID MFTE_MYCS2 Reviewed; 247 AA.
AC A0QSC0;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 2.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Mycofactocin precursor peptide peptidase {ECO:0000305|PubMed:30183269};
DE EC=3.4.14.- {ECO:0000269|PubMed:30183269};
GN Name=mftE {ECO:0000303|PubMed:28077628, ECO:0000303|PubMed:30183269};
GN OrderedLocusNames=MSMEG_1425 {ECO:0000312|EMBL:ABK70622.1};
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 PEPTIDASE ACTIVITY, AND COFACTOR.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=28077628; DOI=10.1074/jbc.m116.762062;
RA Bruender N.A., Bandarian V.;
RT "The Creatininase Homolog MftE from Mycobacterium smegmatis Catalyzes a
RT Peptide Cleavage Reaction in the Biosynthesis of a Novel Ribosomally
RT Synthesized Post-translationally Modified Peptide (RiPP).";
RL J. Biol. Chem. 292:4371-4381(2017).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=30183269; DOI=10.1021/acs.biochem.8b00816;
RA Ayikpoe R., Salazar J., Majestic B., Latham J.A.;
RT "Mycofactocin Biosynthesis Proceeds through 3-Amino-5-[(p-
RT hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP); Direct
RT Observation of MftE Specificity toward MftA.";
RL Biochemistry 57:5379-5383(2018).
RN [4]
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 [5]
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: Peptidase involved in the biosynthesis of the enzyme cofactor
CC mycofactocin (MFT) (PubMed:33014324). Catalyzes cleavage of the MftC-
CC modified MftA peptide to liberate its final two residues, which consist
CC of a cross-linked valine-decarboxylated tyrosine dipeptide (named 3-
CC amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-2-one or
CC ADHP) (PubMed:30183269). Is required for the in vivo ethanol
CC assimilation in M.smegmatis (PubMed:31113891).
CC {ECO:0000269|PubMed:30183269, ECO:0000269|PubMed:31113891,
CC ECO:0000269|PubMed:33014324}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[mycofactocin precursor peptide]-C-terminal glycyl-N-{5-[(4-
CC hydroxyphenyl)methyl]-4,4-dimethyl-2-oxopyrrolidin-3-yl}acetamide +
CC H2O = 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-
CC 2-one + [mycofactocin precursor peptide]-C-terminal glycine;
CC Xref=Rhea:RHEA:65504, Rhea:RHEA-COMP:16818, Rhea:RHEA-COMP:16819,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:83148, ChEBI:CHEBI:150863,
CC ChEBI:CHEBI:156518; Evidence={ECO:0000269|PubMed:30183269};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:28077628};
CC Note=MftE appears to bind one Fe(2+) and one Zn(2+) ion per subunit.
CC Fe(2+) seems to be catalytically active while Zn(2+) could play an
CC auxiliary role. {ECO:0000250|UniProtKB:A0PM51};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:28077628};
CC -!- SUBUNIT: Homooctamer. {ECO:0000250|UniProtKB:A0PM51}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene present delayed growth in
CC ethanol as the sole growth substrate (PubMed:31113891). Glycosylated
CC mycofactocins are produced in this mutant, albeit in significantly
CC lower amounts than wild type. MtfE can likely be complemented by an
CC unknown peptidase present in the metabolic background of mycobacteria
CC (PubMed:33014324). {ECO:0000269|PubMed:31113891,
CC ECO:0000269|PubMed:33014324}.
CC -!- SIMILARITY: Belongs to the creatininase superfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to cleave the C-terminal dipeptide from
CC the first intermediate product formed by the action of MftC on MftA,
CC i.e. MftA modified with a C-terminal glycyl-L-valyl-decarboxylated L-
CC tyrosine (PubMed:28077628). However, it was later shown that the
CC terminal product formed by the action of MftC on MftA is the true
CC substrate of MftE, i.e. MftA modified with a C-terminal glycyl-3-amino-
CC 5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one
CC (PubMed:30183269). {ECO:0000269|PubMed:28077628,
CC ECO:0000269|PubMed:30183269}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABK70622.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CP000480; ABK70622.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_014877069.1; NZ_SIJM01000016.1.
DR RefSeq; YP_885808.1; NC_008596.1.
DR AlphaFoldDB; A0QSC0; -.
DR SMR; A0QSC0; -.
DR STRING; 246196.MSMEI_1390; -.
DR EnsemblBacteria; ABK70622; ABK70622; MSMEG_1425.
DR GeneID; 66732884; -.
DR KEGG; msm:MSMEG_1425; -.
DR PATRIC; fig|246196.19.peg.1412; -.
DR eggNOG; COG1402; Bacteria.
DR Proteomes; UP000000757; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.10310; -; 1.
DR InterPro; IPR024087; Creatininase-like_sf.
DR InterPro; IPR003785; Creatininase/forma_Hydrolase.
DR InterPro; IPR023871; MftE.
DR PANTHER; PTHR35005; PTHR35005; 1.
DR Pfam; PF02633; Creatininase; 1.
DR SUPFAM; SSF102215; SSF102215; 1.
DR TIGRFAMs; TIGR03964; mycofact_creat; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Iron; Metal-binding; Protease; Reference proteome; Zinc.
FT CHAIN 1..247
FT /note="Mycofactocin precursor peptide peptidase"
FT /id="PRO_0000452051"
FT BINDING 38
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P83772"
FT BINDING 40
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P83772"
FT BINDING 49
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P83772"
FT BINDING 49
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P83772"
FT BINDING 124
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P83772"
FT BINDING 163
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P83772"
SQ SEQUENCE 247 AA; 25761 MW; 04E233C78A6481F2 CRC64;
MNSAYHRHVA FPSGLGTSTS RQLHSMVPMV LVPVGSTEQH GPHLPLDTDT RIAAAVAGTV
VEQFGAPADR DAVVAPPVAY GASGEHEGFP GTVSIGTAAL ELLLVEYGRS ASKWTSRIVF
VNGHGGNVEA LAAAVALLRY EGRDAGWVPC SVPDADAHAG HTETSVLLHI SPDDVLTDEL
VCGNTAPLAE LMPRMRSGGV AAVSELGILG DPTTATAAEG ERIFAEMVNG CADRIKRWQP
DRNGLLT
