LANA_ACTGA
ID LANA_ACTGA Reviewed; 64 AA.
AC P56650; C4NFI0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 3.
DT 25-MAY-2022, entry version 58.
DE RecName: Full=Lantibiotic actagardine {ECO:0000303|PubMed:19400806, ECO:0000303|PubMed:2211371, ECO:0000303|PubMed:7737178, ECO:0000303|PubMed:9219543};
DE AltName: Full=Gardimycin;
DE Flags: Precursor;
GN Name=garA {ECO:0000303|PubMed:19400806};
OS Actinoplanes garbadinensis.
OC Bacteria; Actinobacteria; Micromonosporales; Micromonosporaceae;
OC Actinoplanes.
OX NCBI_TaxID=69485;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF SER-47;
RP GLY-48; VAL-50; GLY-58 AND VAL-60.
RC STRAIN=ATCC 31049 / DSM 44321 / JCM 3248 / KCTC 9533 / NBRC 13995 / NCIMB
RC 12637 / NRRL B-16719 / A/10889;
RX PubMed=19400806; DOI=10.1111/j.1365-2958.2009.06708.x;
RA Boakes S., Cortes J., Appleyard A.N., Rudd B.A.M., Dawson M.J.;
RT "Organization of the genes encoding the biosynthesis of actagardine and
RT engineering of a variant generation system.";
RL Mol. Microbiol. 72:1126-1136(2009).
RN [2]
RP PRELIMINARY PROTEIN SEQUENCE OF 47-64, AND STRUCTURE BY NMR OF 47-64.
RC STRAIN=ATCC 31049 / DSM 44321 / JCM 3248 / KCTC 9533 / NBRC 13995 / NCIMB
RC 12637 / NRRL B-16719 / A/10889;
RX PubMed=2211371; DOI=10.7164/antibiotics.43.1082;
RA Kettenring J.K., Malabarba A., Vekey K., Cavalleri B.;
RT "Sequence determination of actagardine, a novel lantibiotic, by homonuclear
RT 2D NMR spectroscopy.";
RL J. Antibiot. 43:1082-1088(1990).
RN [3]
RP PROTEIN SEQUENCE OF 47-64, STRUCTURE BY NMR OF 47-64, AND CROSS-LINK.
RC STRAIN=ATCC 31049 / DSM 44321 / JCM 3248 / KCTC 9533 / NBRC 13995 / NCIMB
RC 12637 / NRRL B-16719 / A/10889;
RX PubMed=7737178; DOI=10.1111/j.1432-1033.1995.0786m.x;
RA Zimmermann N., Metzger J.W., Jung G.;
RT "The tetracyclic lantibiotic actagardine. 1H-NMR and 13C-NMR assignments
RT and revised primary structure.";
RL Eur. J. Biochem. 228:786-797(1995).
RN [4]
RP FUNCTION.
RX PubMed=9449277; DOI=10.1128/aac.42.1.154;
RA Broetz H., Bierbaum G., Leopold K., Reynolds P.E., Sahl H.G.;
RT "The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting
RT lipid II.";
RL Antimicrob. Agents Chemother. 42:154-160(1998).
RN [5]
RP STRUCTURE BY NMR OF 47-64, AND CROSS-LINK.
RX PubMed=9219543; DOI=10.1111/j.1432-1033.1997.00809.x;
RA Zimmermann N., Jung G.;
RT "The three-dimensional solution structure of the lantibiotic murein-
RT biosynthesis-inhibitor actagardine determined by NMR.";
RL Eur. J. Biochem. 246:809-819(1997).
CC -!- FUNCTION: Has potent antibacterial activity against some Gram-positive
CC bacteria (PubMed:19400806). Has good antistreptococcal activity.
CC Inhibits cell wall biosynthesis by binding to lipid II and blocking
CC transglycosylation (PubMed:9449277). {ECO:0000269|PubMed:19400806,
CC ECO:0000269|PubMed:9449277}.
CC -!- PTM: Maturation of lantibiotics involves the enzymatic conversion of
CC Thr, and Ser into dehydrated AA by the enzyme garM and the formation of
CC thioether bonds with cysteine (Probable). The 59-64 beta-
CC methyllanthionine thioether bond is oxidized to a sulfoxide by the
CC monooxygenase GarO (PubMed:19400806). This is followed by membrane
CC translocation and cleavage of the modified precursor (Probable).
CC {ECO:0000269|PubMed:19400806, ECO:0000305|PubMed:19400806}.
CC -!- PTM: The sulfoxide group of the 59-64 beta-methyllanthionine thioether
CC bond is mildly important for activity, since the antibacterial activity
CC of deoxyactagardine is marginally lower compared with oxidized
CC actagardine. {ECO:0000269|PubMed:19400806}.
CC -!- SIMILARITY: Belongs to the type B lantibiotic family. {ECO:0000305}.
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DR EMBL; FJ547091; ACR33052.1; -; Genomic_DNA.
DR PIR; A58700; A58700.
DR PDB; 1AJ1; NMR; -; A=47-64.
DR PDBsum; 1AJ1; -.
DR AlphaFoldDB; P56650; -.
DR SMR; P56650; -.
DR EvolutionaryTrace; P56650; -.
DR GO; GO:0005102; F:signaling receptor binding; IEA:UniProtKB-KW.
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; Lantibiotic; Oxidation; Thioether bond.
FT PROPEP 1..45
FT /evidence="ECO:0000269|PubMed:7737178"
FT /id="PRO_0000450805"
FT PEPTIDE 46..64
FT /note="Lantibiotic actagardine"
FT /evidence="ECO:0000269|PubMed:7737178"
FT /id="PRO_0000043967"
FT CROSSLNK 46..51
FT /note="Lanthionine (Ser-Cys)"
FT /evidence="ECO:0000269|PubMed:7737178,
FT ECO:0000269|PubMed:9219543"
FT CROSSLNK 52..57
FT /note="Beta-methyllanthionine (Thr-Cys)"
FT /evidence="ECO:0000269|PubMed:7737178,
FT ECO:0000269|PubMed:9219543"
FT CROSSLNK 54..62
FT /note="Beta-methyllanthionine (Thr-Cys)"
FT /evidence="ECO:0000269|PubMed:7737178,
FT ECO:0000269|PubMed:9219543"
FT CROSSLNK 59..64
FT /note="Beta-methyllanthionine sulfoxide (Thr-Cys)"
FT /evidence="ECO:0000269|PubMed:7737178,
FT ECO:0000269|PubMed:9219543"
FT MUTAGEN 47
FT /note="S->A: Decrease in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:19400806"
FT MUTAGEN 48
FT /note="G->A: Loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:19400806"
FT MUTAGEN 50
FT /note="V->A: Loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:19400806"
FT MUTAGEN 58
FT /note="G->A: Loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:19400806"
FT MUTAGEN 60
FT /note="V->A: Decrease in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:19400806"
FT STRAND 52..62
FT /evidence="ECO:0007829|PDB:1AJ1"
SQ SEQUENCE 64 AA; 6883 MW; 42C3E9945D459B11 CRC64;
MSALAIEKSW KDVDLRDGAT SHPAGLGFGE LTFEDLREDR TIYAASSGWV CTLTIECGTV
ICAC
