MCJA_ECOLX
ID MCJA_ECOLX Reviewed; 58 AA.
AC Q9X2V7;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 25-MAY-2022, entry version 89.
DE RecName: Full=Microcin J25 {ECO:0000303|PubMed:1429464};
DE Short=MccJ25 {ECO:0000303|PubMed:1429464};
DE AltName: Full=Class II lasso peptide {ECO:0000303|PubMed:30626643};
DE AltName: Full=Ribosomally synthesized and post-translationally modified peptide {ECO:0000303|PubMed:30626643};
DE Short=RiPP {ECO:0000303|PubMed:30626643};
DE Flags: Precursor;
GN Name=mcjA;
OS Escherichia coli.
OG Plasmid pTUC100.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=AY25;
RX PubMed=10198038; DOI=10.1128/jb.181.8.2659-2662.1999;
RA Solbiati J.O., Ciaccio M., Farias R.N., Gonzalez-Pastor J.E., Moreno F.,
RA Salomon R.A.;
RT "Sequence analysis of the four plasmid genes required to produce the
RT circular peptide antibiotic microcin J25.";
RL J. Bacteriol. 181:2659-2662(1999).
RN [2]
RP PROTEIN SEQUENCE OF 38-58, AND MASS SPECTROMETRY.
RX PubMed=10092860; DOI=10.1046/j.1432-1327.1999.00085.x;
RA Blond A., Peduzzi J., Goulard C., Chiuchiolo M.J., Barthelemy M.,
RA Prigent Y., Salomon R.A., Farias R.N., Moreno F., Rebuffat S.;
RT "The cyclic structure of microcin J25, a 21-residue peptide antibiotic from
RT Escherichia coli.";
RL Eur. J. Biochem. 259:747-755(1999).
RN [3]
RP FUNCTION.
RX PubMed=1429464; DOI=10.1128/jb.174.22.7428-7435.1992;
RA Salomon R.A., Farias R.N.;
RT "Microcin 25, a novel antimicrobial peptide produced by Escherichia coli.";
RL J. Bacteriol. 174:7428-7435(1992).
RN [4]
RP FUNCTION.
RX PubMed=11731133; DOI=10.1111/j.1574-6968.2001.tb10895.x;
RA Rintoul M.R., de Arcuri B.F., Salomon R.A., Farias R.N., Morero R.D.;
RT "The antibacterial action of microcin J25: evidence for disruption of
RT cytoplasmic membrane energization in Salmonella newport.";
RL FEMS Microbiol. Lett. 204:265-270(2001).
RN [5]
RP FUNCTION.
RX PubMed=11443089; DOI=10.1128/jb.183.15.4543-4550.2001;
RA Delgado M.A., Rintoul M.R., Farias R.N., Salomon R.A.;
RT "Escherichia coli RNA polymerase is the target of the cyclopeptide
RT antibiotic microcin J25.";
RL J. Bacteriol. 183:4543-4550(2001).
RN [6]
RP FUNCTION.
RX PubMed=12401787; DOI=10.1074/jbc.m209425200;
RA Yuzenkova J., Delgado M.A., Nechaev S., Savalia D., Epshtein V.,
RA Artsimovitch I., Mooney R.A., Landick R., Farias R.N., Salomon R.A.,
RA Severinov K.;
RT "Mutations of bacterial RNA polymerase leading to resistance to microcin
RT J25.";
RL J. Biol. Chem. 277:50867-50875(2002).
RN [7]
RP FUNCTION.
RX PubMed=15200952; DOI=10.1016/j.molcel.2004.06.010;
RA Mukhopadhyay J., Sineva E., Knight J., Levy R.M., Ebright R.H.;
RT "Antibacterial peptide microcin J25 inhibits transcription by binding
RT within and obstructing the RNA polymerase secondary channel.";
RL Mol. Cell 14:739-751(2004).
RN [8]
RP MUTAGENESIS OF GLY-41; PRO-44; TYR-46; PHE-47; ILE-50; THR-52; PHE-56 AND
RP TYR-57.
RX PubMed=18632663; DOI=10.1074/jbc.m803995200;
RA Pavlova O., Mukhopadhyay J., Sineva E., Ebright R.H., Severinov K.;
RT "Systematic structure-activity analysis of microcin J25.";
RL J. Biol. Chem. 283:25589-25595(2008).
RN [9]
RP STRUCTURE BY NMR OF 38-58, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14531661; DOI=10.1021/ja036677e;
RA Bayro M.J., Mukhopadhyay J., Swapna G.V.T., Huang J.Y., Ma L.-C.,
RA Sineva E., Dawson P.E., Montelione G.T., Ebright R.H.;
RT "Structure of antibacterial peptide microcin J25: a 21-residue lariat
RT protoknot.";
RL J. Am. Chem. Soc. 125:12382-12383(2003).
RN [10]
RP STRUCTURE BY NMR OF 38-58, CHARACTERIZATION, AND MASS SPECTROMETRY.
RX PubMed=14531690; DOI=10.1021/ja0367703;
RA Rosengren K.J., Clark R.J., Daly N.L., Goeransson U., Jones A., Craik D.J.;
RT "Microcin J25 has a threaded sidechain-to-backbone ring structure and not a
RT head-to-tail cyclized backbone.";
RL J. Am. Chem. Soc. 125:12464-12474(2003).
RN [11]
RP STRUCTURE BY NMR OF 38-58, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14531691; DOI=10.1021/ja036756q;
RA Wilson K.-A., Kalkum M., Ottesen J., Yuzenkova J., Chait B.T., Landick R.,
RA Muir T., Severinov K., Darst S.A.;
RT "Structure of microcin J25, a peptide inhibitor of bacterial RNA
RT polymerase, is a lassoed tail.";
RL J. Am. Chem. Soc. 125:12475-12483(2003).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.68 ANGSTROMS) OF 38-58 IN COMPLEX WITH E.COLI RNA
RP POLYMERASE, AND FUNCTION.
RX PubMed=30626643; DOI=10.1073/pnas.1817352116;
RA Braffman N.R., Piscotta F.J., Hauver J., Campbell E.A., Link A.J.,
RA Darst S.A.;
RT "Structural mechanism of transcription inhibition by lasso peptides
RT microcin J25 and capistruin.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:1273-1278(2019).
CC -!- FUNCTION: Peptide antibiotic that functions through inhibition of the
CC bacterial DNA-dependent RNA polymerase (RNAP) (PubMed:11443089,
CC PubMed:12401787). Inhibits transcription by binding deep within RNAP
CC secondary channel, where it sterically blocks the folding of the
CC trigger loop, which is essential for efficient catalysis
CC (PubMed:15200952, PubMed:30626643). In addition, it also seems to
CC restrict access of nucleotide substrates to the catalytic center, and
CC shows a partially competitive mode of inhibition with them
CC (PubMed:15200952, PubMed:30626643). Exhibits potent bacteriocidal
CC activity against a range of Enterobacteriaceae, including several
CC pathogenic E.coli, Salmonella and Shigella strains (PubMed:1429464).
CC Also acts on the cytoplasmic membrane of Salmonella newport, producing
CC alteration of membrane permeability and disruption of the subsequent
CC gradient dissipation, which inhibits several processes essential for
CC cell viability, such as oxygen consumption (PubMed:11731133). Induces
CC bacterial filamentation in susceptible cells in a non-SOS-dependent
CC way, but this phenotype may result from impaired transcription of genes
CC coding for cell division proteins (PubMed:1429464).
CC {ECO:0000269|PubMed:11443089, ECO:0000269|PubMed:11731133,
CC ECO:0000269|PubMed:12401787, ECO:0000269|PubMed:1429464,
CC ECO:0000269|PubMed:15200952, ECO:0000269|PubMed:30626643}.
CC -!- INTERACTION:
CC Q9X2V7; P06971: fhuA; Xeno; NbExp=2; IntAct=EBI-16100378, EBI-1116714;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:18632663}.
CC -!- INDUCTION: At the onset of stationary growth phase.
CC {ECO:0000269|PubMed:1429464}.
CC -!- MASS SPECTROMETRY: Mass=2107.0; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10092860};
CC -!- MASS SPECTROMETRY: Mass=2106.0; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:14531690};
CC -!- CAUTION: Was originally thought to have a head-to-tail cyclic
CC structure, but actually has a threaded side chain-to-backbone ring
CC structure that is penetrated by the C-terminal tail in a noose-like
CC motif. {ECO:0000305|PubMed:10092860}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Entanglement - Issue 72 of
CC July 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/072";
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DR EMBL; AF061787; AAD28494.1; -; Genomic_DNA.
DR RefSeq; WP_001513516.1; NZ_WVVR01000053.1.
DR RefSeq; YP_009071192.1; NC_025179.1.
DR PDB; 1PP5; NMR; -; A=38-58.
DR PDB; 1Q71; NMR; -; A=38-58.
DR PDB; 1S7P; NMR; -; A=38-47, B=48-58.
DR PDB; 2MMT; NMR; -; A=38-58.
DR PDB; 2MMW; NMR; -; A=38-58.
DR PDB; 4CU4; X-ray; 2.30 A; B=38-58.
DR PDB; 6N60; X-ray; 3.68 A; M=38-58.
DR PDBsum; 1PP5; -.
DR PDBsum; 1Q71; -.
DR PDBsum; 1S7P; -.
DR PDBsum; 2MMT; -.
DR PDBsum; 2MMW; -.
DR PDBsum; 4CU4; -.
DR PDBsum; 6N60; -.
DR AlphaFoldDB; Q9X2V7; -.
DR BMRB; Q9X2V7; -.
DR PCDDB; Q9X2V7; -.
DR SMR; Q9X2V7; -.
DR DIP; DIP-60856N; -.
DR IntAct; Q9X2V7; 1.
DR TCDB; 9.A.52.1.1; the microcin j25 (microsin j25) family.
DR EvolutionaryTrace; Q9X2V7; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Bacteriocin;
KW Direct protein sequencing; Isopeptide bond; Plasmid; Secreted.
FT PROPEP 1..37
FT /evidence="ECO:0000269|PubMed:10092860"
FT /id="PRO_0000002774"
FT PEPTIDE 38..58
FT /note="Microcin J25"
FT /evidence="ECO:0000269|PubMed:10092860"
FT /id="PRO_0000002775"
FT SITE 41
FT /note="Essential for permeation into bacteria"
FT /evidence="ECO:0000269|PubMed:18632663"
FT SITE 44
FT /note="Essential for permeation into bacteria"
FT /evidence="ECO:0000269|PubMed:18632663"
FT SITE 46
FT /note="Essential for permeation into bacteria and for RNAP
FT inhibition"
FT /evidence="ECO:0000269|PubMed:18632663"
FT SITE 47
FT /note="Essential for permeation into bacteria"
FT /evidence="ECO:0000269|PubMed:18632663"
FT SITE 56
FT /note="Essential for permeation into bacteria"
FT /evidence="ECO:0000269|PubMed:18632663"
FT SITE 57
FT /note="Essential for permeation into bacteria"
FT /evidence="ECO:0000269|PubMed:18632663"
FT CROSSLNK 38..45
FT /note="Isoglutamyl glycine isopeptide (Gly-Glu)"
FT /evidence="ECO:0000269|PubMed:14531661,
FT ECO:0000269|PubMed:14531690, ECO:0000269|PubMed:14531691"
FT MUTAGEN 41
FT /note="G->A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,T,V,W,Y: Loss of
FT RNAP inhibition and loss of bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 41
FT /note="G->S: No change of RNAP inhibition but loss of
FT bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 44
FT /note="P->A,L,V: No change of RNAP inhibition but loss of
FT bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 44
FT /note="P->C,D,E,F,G,H,I,K,M,N,P,Q,R,S,T,W,Y: Loss of RNAP
FT inhibition and loss of bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 46
FT /note="Y->A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y: Loss of
FT RNAP inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 47
FT /note="F->A,C,D,E,F,G,H,K,L,N,P,Q,T,V,Y: Loss of RNAP
FT inhibition and loss of bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 47
FT /note="F->I,M,R,S,W: No change of RNAP inhibition but loss
FT of bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 50
FT /note="I->A,L,M,N,P,R,T: Increase in bacterial growth
FT inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 52
FT /note="T->A,F,H,L: Increase in bacterial growth
FT inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 52
FT /note="T->G: No change of RNAP inhibition but increase in
FT permeation into bacterial cells and bacterial growth
FT inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 56
FT /note="F->A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V: Loss of RNAP
FT inhibition and loss of bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 56
FT /note="F->W,Y: No change of RNAP inhibition but loss of
FT bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 57
FT /note="Y->A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y: Loss
FT RNAP inhibition, and loss of bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT MUTAGEN 57
FT /note="Y->F: No change of RNAP inhibition, and loss of
FT bacterial growth inhibition."
FT /evidence="ECO:0000269|PubMed:18632663"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:4CU4"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:1PP5"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:1PP5"
SQ SEQUENCE 58 AA; 6200 MW; A9F4393C8EAAC8FA CRC64;
MIKHFHFNKL SSGKKNNVPS PAKGVIQIKK SASQLTKGGA GHVPEYFVGI GTPISFYG
