LANA_STRMG
ID LANA_STRMG Reviewed; 53 AA.
AC O54329; P84110;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 60.
DE RecName: Full=Lantibiotic mutacin-2;
DE AltName: Full=Lantibiotic mutacin H-29B;
DE AltName: Full=Mutacin II;
DE Flags: Precursor;
GN Name=mutA {ECO:0000312|EMBL:AAC38144.1};
OS Streptococcus mutans.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=1309;
RN [1] {ECO:0000312|EMBL:AAC38144.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=T8 {ECO:0000312|EMBL:AAC38144.1};
RX PubMed=9461412; DOI=10.1016/s0378-1119(97)00578-7;
RA Woodruff W.A., Novak J., Caufield P.W.;
RT "Sequence analysis of mutA and mutM genes involved in the biosynthesis of
RT the lantibiotic mutacin II in Streptococcus mutans.";
RL Gene 206:37-43(1998).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 27-50, DEHYDRATION AT THR-51, LANTHIONINE CROSS-LINKS,
RP AND MUTAGENESIS OF CYS-41 AND CYS-52.
RC STRAIN=T8 {ECO:0000269|PubMed:10821848};
RX PubMed=10821848; DOI=10.1074/jbc.275.21.15845;
RA Krull R.E., Chen P., Novak J., Kirk M., Barnes S., Baker J., Krishna N.R.,
RA Caufield P.W.;
RT "Biochemical structural analysis of the lantibiotic mutacin II.";
RL J. Biol. Chem. 275:15845-15850(2000).
RN [3]
RP PROTEIN SEQUENCE OF 27-50, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MASS
RP SPECTROMETRY, AND POST-TRANSLATIONAL MODIFICATIONS.
RC STRAIN=29B;
RX PubMed=16626493; DOI=10.1186/1471-2180-6-36;
RA Nicolas G., Morency H., LaPointe G., Lavoie M.C.;
RT "Mutacin H-29B is identical to mutacin II (J-T8).";
RL BMC Microbiol. 6:36-36(2006).
RN [4] {ECO:0000305}
RP PROTEIN SEQUENCE OF 27-37, POST-TRANSLATIONAL MODIFICATIONS, AND
RP MUTAGENESIS OF ASN-27; VAL-33; PRO-35; THR-36; CYS-41; CYS-52 AND CYS-53.
RC STRAIN=T8 {ECO:0000269|PubMed:9647795};
RX PubMed=9647795; DOI=10.1128/aem.64.7.2335-2340.1998;
RA Chen P., Novak J., Kirk M., Barnes S., Qi F., Caufield P.W.;
RT "Structure-activity study of the lantibiotic mutacin II from Streptococcus
RT mutans T8 by a gene replacement strategy.";
RL Appl. Environ. Microbiol. 64:2335-2340(1998).
RN [5] {ECO:0000305}
RP PROTEIN SEQUENCE OF 27-34, FUNCTION, POST-TRANSLATIONAL MODIFICATIONS, MASS
RP SPECTROMETRY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=T8 {ECO:0000269|PubMed:8021218};
RX PubMed=8021218; DOI=10.1128/jb.176.14.4316-4320.1994;
RA Novak J., Caufield P.W., Miller E.J.;
RT "Isolation and biochemical characterization of a novel lantibiotic mutacin
RT from Streptococcus mutans.";
RL J. Bacteriol. 176:4316-4320(1994).
RN [6] {ECO:0000305}
RP FUNCTION.
RC STRAIN=T8 {ECO:0000269|PubMed:8592997};
RX PubMed=8592997; DOI=10.1128/aac.39.12.2656;
RA Chikindas M.L., Novak J., Driessen A.J.M., Konings W.N., Schilling K.M.,
RA Caufield P.W.;
RT "Mutacin II, a bactericidal lantibiotic from Streptococcus mutans.";
RL Antimicrob. Agents Chemother. 39:2656-2660(1995).
RN [7] {ECO:0000305}
RP POST-TRANSLATIONAL MODIFICATIONS, AND MASS SPECTROMETRY.
RC STRAIN=T8 {ECO:0000269|PubMed:8660519};
RX PubMed=8660519; DOI=10.1006/abio.1996.0181;
RA Novak J., Kirk M., Caufield P.W., Barnes S., Morrison K., Baker J.;
RT "Detection of modified amino acids in lantibiotic peptide mutacin II by
RT chemical derivation and electrospray ionization-mass spectroscopic
RT analysis.";
RL Anal. Biochem. 236:358-360(1996).
RN [8] {ECO:0000305}
RP MUTAGENESIS OF GLU-14; VAL-15; SER-16; GLU-19; LEU-20; ILE-23; GLY-25 AND
RP GLY-26.
RC STRAIN=T8 {ECO:0000269|PubMed:11179642};
RX PubMed=11179642; DOI=10.1111/j.1574-6968.2001.tb10511.x;
RA Chen P., Qi F., Novak J., Krull R.E., Caufield P.W.;
RT "Effect of amino acid substitutions in conserved residues in the leader
RT peptide on biosynthesis of the lantibiotic mutacin II.";
RL FEMS Microbiol. Lett. 195:139-144(2001).
CC -!- FUNCTION: Lanthionine-containing peptide antibiotic (lantibiotic)
CC active on Gram-positive bacteria including M.luteus, S.aureus,
CC Streptococcus, P.micros, P.acidilactici, C.sporogenes, C.diphtheriae,
CC A.viscosus, G.vaginalis, P.acnes, L.monocytogenes and M.smegmatis, and
CC Gram-negative bacteria including C.jejuni, H.pylori and N.gonorrhoeae.
CC Transiently and partially depolarizes the transmembrane electrical
CC potential and pH gradient of susceptible cells, inhibits the uptake of
CC amino acids and depletes the intracellular ATP pool.
CC {ECO:0000269|PubMed:16626493, ECO:0000269|PubMed:8021218,
CC ECO:0000269|PubMed:8592997}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Stable from pH 2.0 to 4.0. Activity decreases gradually with
CC increasing pH. {ECO:0000269|PubMed:16626493,
CC ECO:0000269|PubMed:8021218};
CC Temperature dependence:
CC Thermostable. {ECO:0000269|PubMed:16626493,
CC ECO:0000269|PubMed:8021218};
CC -!- PTM: Maturation of lantibiotics involves the enzymatic conversion of
CC Thr, and Ser into dehydrated AA and the formation of thioether bonds
CC with cysteine. This is followed by membrane translocation and cleavage
CC of the modified precursor. {ECO:0000305}.
CC -!- PTM: It is not established whether the 2,3-didehydrobutyrine is the
CC E- or Z-isomer (PubMed:10821848, PubMed:16626493, PubMed:9647795,
CC PubMed:8021218 and PubMed:8660519).
CC -!- MASS SPECTROMETRY: Mass=3244.64; Mass_error=1.15; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:8021218};
CC -!- MASS SPECTROMETRY: Mass=3245.4; Mass_error=0.58; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:8660519};
CC -!- MASS SPECTROMETRY: Mass=3246.08; Mass_error=0.1; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:16626493};
CC -!- SIMILARITY: Belongs to the type A lantibiotic family. {ECO:0000255}.
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DR EMBL; U40620; AAC38144.1; -; Genomic_DNA.
DR PIR; JC6526; JC6526.
DR AlphaFoldDB; O54329; -.
DR TCDB; 1.C.21.1.10; the lacticin 481 (lacticin 481) family.
DR GO; GO:0005576; C:extracellular region; IC:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IEA:UniProtKB-KW.
DR GO; GO:0006865; P:amino acid transport; IDA:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:UniProtKB.
DR InterPro; IPR007682; Lantibiotic_typ-A_Lactobact.
DR Pfam; PF04604; L_biotic_typeA; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Bacteriocin; Direct protein sequencing;
KW Lantibiotic; Thioether bond.
FT PROPEP 1..26
FT /evidence="ECO:0000269|PubMed:10821848,
FT ECO:0000269|PubMed:16626493, ECO:0000269|PubMed:8021218,
FT ECO:0000269|PubMed:9647795"
FT /id="PRO_0000017128"
FT PEPTIDE 27..53
FT /note="Lantibiotic mutacin-2"
FT /id="PRO_0000017129"
FT MOD_RES 51
FT /note="2,3-didehydrobutyrine"
FT /evidence="ECO:0000269|PubMed:10821848"
FT CROSSLNK 36..41
FT /note="Beta-methyllanthionine (Thr-Cys)"
FT /evidence="ECO:0000269|PubMed:10821848"
FT CROSSLNK 38..52
FT /note="Lanthionine (Ser-Cys)"
FT /evidence="ECO:0000269|PubMed:10821848"
FT CROSSLNK 45..53
FT /note="Lanthionine (Ser-Cys)"
FT /evidence="ECO:0000269|PubMed:10821848"
FT MUTAGEN 14
FT /note="E->D: No loss of activity or protein production."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 14
FT /note="E->K: Reduced protein production to about 10% of
FT wild-type level."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 15
FT /note="V->I,A: No loss of activity or protein production."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 15
FT /note="V->L: Reduced protein production to about 50% of
FT wild-type level."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 16
FT /note="S->T,A: No loss of activity or protein production."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 19
FT /note="E->D: No loss of activity or protein production."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 19
FT /note="E->K: Reduced protein production to about 75% of
FT wild-type level."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 20
FT /note="L->K: No mature protein is produced."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 20
FT /note="L->M: No loss of activity or protein production."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 23
FT /note="I->D: No mature protein is produced."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 23
FT /note="I->V: No loss of activity or protein production."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 25
FT /note="G->A: No mature protein is produced."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 26
FT /note="G->A: No mature protein is produced."
FT /evidence="ECO:0000269|PubMed:11179642"
FT MUTAGEN 27
FT /note="Missing: No protein is secreted."
FT /evidence="ECO:0000269|PubMed:9647795"
FT MUTAGEN 33
FT /note="V->A: No loss of activity."
FT /evidence="ECO:0000269|PubMed:9647795"
FT MUTAGEN 35
FT /note="P->A: Low activity, less than 10% of wild-type."
FT /evidence="ECO:0000269|PubMed:9647795"
FT MUTAGEN 36
FT /note="T->A: Loss of secretion."
FT /evidence="ECO:0000269|PubMed:9647795"
FT MUTAGEN 36
FT /note="T->S: No loss of activity."
FT /evidence="ECO:0000269|PubMed:9647795"
FT MUTAGEN 41
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10821848,
FT ECO:0000269|PubMed:9647795"
FT MUTAGEN 52
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10821848,
FT ECO:0000269|PubMed:9647795"
FT MUTAGEN 53
FT /note="C->A: Low activity, less than 10% of wild-type
FT level."
FT /evidence="ECO:0000269|PubMed:9647795"
SQ SEQUENCE 53 AA; 6020 MW; 6C3788E2C9EC6525 CRC64;
MNKLNSNAVV SLNEVSDSEL DTILGGNRWW QGVVPTVSYE CRMNSWQHVF TCC