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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
 
 
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