NOSM_STRAS
ID NOSM_STRAS Reviewed; 50 AA.
AC C6FX52;
DT 14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 1.
DT 25-MAY-2022, entry version 22.
DE RecName: Full=Nosiheptide precursor {ECO:0000303|PubMed:19678698};
DE Contains:
DE RecName: Full=Nosiheptide {ECO:0000303|PubMed:19678698};
DE Short=NOS {ECO:0000303|PubMed:19678698};
DE AltName: Full=Antibiotic 9671-RP {ECO:0000303|PubMed:7379912};
DE AltName: Full=Multhiomycin {ECO:0000303|PubMed:7038038};
GN Name=nosM {ECO:0000312|EMBL:ACR48342.1};
OS Streptomyces actuosus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1885;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ACR48342.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], HYDROXYLATION AT GLU-43, AND MASS
RP SPECTROMETRY.
RC STRAIN=ATCC 25421 / DSM 40337 / JCM 4445 / NBRC 13009 / NRRL 2954 / VKM
RC Ac-1274 {ECO:0000269|PubMed:19678698};
RX PubMed=19678698; DOI=10.1021/cb900133x;
RA Yu Y., Duan L., Zhang Q., Liao R., Ding Y., Pan H., Wendt-Pienkowski E.,
RA Tang G., Shen B., Liu W.;
RT "Nosiheptide biosynthesis featuring a unique indole side ring formation on
RT the characteristic thiopeptide framework.";
RL ACS Chem. Biol. 4:855-864(2009).
RN [2] {ECO:0000305}
RP FUNCTION.
RC STRAIN=ATCC 25421 / DSM 40337 / JCM 4445 / NBRC 13009 / NRRL 2954 / VKM
RC Ac-1274 {ECO:0000269|PubMed:7379912};
RX PubMed=7379912; DOI=10.1007/bf01975121;
RA Benazet F., Cartier M., Florent J., Godard C., Jung G., Lunel J., Mancy D.,
RA Pascal C., Renaut J., Tarridec P., Theilleux J., Tissier R., Dubost M.,
RA Ninet L.;
RT "Nosiheptide, a sulfur-containing peptide antibiotic isolated from
RT Streptomyces actuosus 40037.";
RL Experientia 36:414-416(1980).
RN [3] {ECO:0000305}
RP FUNCTION.
RC STRAIN=ATCC 25421 / DSM 40337 / JCM 4445 / NBRC 13009 / NRRL 2954 / VKM
RC Ac-1274 {ECO:0000269|PubMed:7038038};
RX PubMed=7038038; DOI=10.1099/00221287-126-1-185;
RA Cundliffe E., Thompson J.;
RT "The mode of action of nosiheptide (multhiomycin) and the mechanism of
RT resistance in the producing organism.";
RL J. Gen. Microbiol. 126:185-192(1981).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=12954336; DOI=10.1016/s1074-5521(03)00173-x;
RA Lentzen G., Klinck R., Matassova N., Aboul-ela F., Murchie A.I.;
RT "Structural basis for contrasting activities of ribosome binding thiazole
RT antibiotics.";
RL Chem. Biol. 10:769-778(2003).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=18380436; DOI=10.1021/ja710608w;
RA Baumann S., Schoof S., Harkal S.D., Arndt H.D.;
RT "Mapping the binding site of thiopeptide antibiotics by proximity-induced
RT covalent capture.";
RL J. Am. Chem. Soc. 130:5664-5666(2008).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=20441189; DOI=10.1021/ja909317n;
RA Baumann S., Schoof S., Bolten M., Haering C., Takagi M., Shin-ya K.,
RA Arndt H.D.;
RT "Molecular determinants of microbial resistance to thiopeptide
RT antibiotics.";
RL J. Am. Chem. Soc. 132:6973-6981(2010).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=21836384; DOI=10.1292/jvms.11-0051;
RA Okada Y., Okutani A., Suzuki H., Asakura H., Monden S., Nakama A.,
RA Maruyama T., Igimi S.;
RT "Antimicrobial susceptibilities of Listeria monocytogenes isolated in
RT Japan.";
RL J. Vet. Med. Sci. 73:1681-1684(2011).
RN [8] {ECO:0000305}
RP MASS SPECTROMETRY, AND AMIDATION AT SER-49.
RC STRAIN=ATCC 25421 / DSM 40337 / JCM 4445 / NBRC 13009 / NRRL 2954 / VKM
RC Ac-1274 {ECO:0000269|PubMed:21047073};
RX PubMed=21047073; DOI=10.1021/ja106571g;
RA Yu Y., Guo H., Zhang Q., Duan L., Ding Y., Liao R., Lei C., Shen B.,
RA Liu W.;
RT "NosA catalyzing carboxyl-terminal amide formation in nosiheptide
RT maturation via an enamine dealkylation on the serine-extended precursor
RT peptide.";
RL J. Am. Chem. Soc. 132:16324-16326(2010).
RN [9] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY OF 38-49, AND DEHYDRATION AT SER-49.
RX PubMed=893891; DOI=10.1021/ja00461a039;
RA Pascard C., Ducruix A., Lunel J., Prange T.;
RT "Highly modified cysteine-containing antibiotics. Chemical structure and
RT configuration of nosiheptide.";
RL J. Am. Chem. Soc. 99:6418-6423(1977).
RN [10] {ECO:0000305}
RP STRUCTURE BY NMR, AND DEHYDRATION AT SER-49.
RX PubMed=2584148; DOI=10.7164/antibiotics.42.1643;
RA Mocek U., Chen L.C., Keller P.J., Houck D.R., Beale J.M., Floss H.G.;
RT "1H and 13C NMR assignments of the thiopeptide antibiotic nosiheptide.";
RL J. Antibiot. 42:1643-1648(1989).
RN [11] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) OF 38-49, AND DEHYDRATION AT SER-49.
RX PubMed=18406324; DOI=10.1016/j.molcel.2008.01.009;
RA Harms J.M., Wilson D.N., Schluenzen F., Connell S.R., Stachelhaus T.,
RA Zaborowska Z., Spahn C.M., Fucini P.;
RT "Translational regulation via L11: molecular switches on the ribosome
RT turned on and off by thiostrepton and micrococcin.";
RL Mol. Cell 30:26-38(2008).
CC -!- FUNCTION: Inhibits bacterial protein biosynthesis by binding to
CC ribosomes. Specifically, binds to the complex of 23S rRNA and ribosomal
CC protein L11 (RPLK) in the 50S ribosomal subunit. While allowing a weak
CC binding of elongation factor G (EF-G) to the ribosome and subsequent
CC GTP-hydrolysis, probably impairs conformational changes in both the
CC ribosome and EF-G which are necessary for translocation. In vitro,
CC inhibits Gram-positive bacteria S.aureus strain 209P (MIC=0.0009
CC ug/ml), S.aureus strain 133 (MIC=0.0019 ug/ml), S.aureus strain B3
CC (MIC=0.003 ug/ml), S.aureus strain Hb (MIC=0.003 ug/ml), M.citreus
CC strain ATCC 8411 (MIC=0.0038 ug/ml), M.lysodeikticus strain ATCC 4698
CC (MIC=0.003 ug/ml), S.lutea strain ATCC 9341 (MIC=0.0011 ug/ml),
CC S.faecalis strain ATCC 9790 (MIC=0.0007 ug/ml), S.viridans (MIC=0.0065
CC ug/ml), S.pyogenes hemolyticus strain Dig7 (MIC=0.00028 ug/ml),
CC D.pneumoniae strain Til (MIC=0.00015 ug/ml), N.catrrhalis (MIC=0.0017
CC ug/ml), L.casei strain ATCC 6633 (MIC=0.003 ug/ml), B.cereus strain
CC ATCC 6630 (MIC=0.0071 ug/ml) and various isolates of L.monocytogenes.
CC In vitro, inhibits Gram-negative bacterium P.multocida strain A125
CC (MIC=0.0024 ug/ml) but not M.smegmatis strain ATCC 6630, S.typhimurium,
CC A.aerogenes strain ATCC 8308, P.vulgaris, K.pneumoniae strain ATCC
CC 10031, S.marcescens strain A476, P.aeruginosa strain Bass or
CC B.bronchiseptica strain CN387. Does not inhibit Gram-negative bacterium
CC E.coli strain ATCC 9637 but does inhibit purified ribosomes from
CC E.coli. In vivo, has no systemic effect in mice infected with
CC staphylococci or streptococci when applied orally or subcutaneously.
CC Has a local effect in mice infected subcutaneously or intraperitoneally
CC with staphylococci when applied immediately afterwards. Is not toxic to
CC mice. {ECO:0000269|PubMed:12954336, ECO:0000269|PubMed:18380436,
CC ECO:0000269|PubMed:18406324, ECO:0000269|PubMed:20441189,
CC ECO:0000269|PubMed:21836384, ECO:0000269|PubMed:7038038,
CC ECO:0000269|PubMed:7379912}.
CC -!- PTM: The amidation of Ser-49 is produced by the oxidative cleavage of
CC Ser-50 rather than of a glycine, as in eukaryotes.
CC {ECO:0000269|PubMed:21047073}.
CC -!- MASS SPECTROMETRY: [Nosiheptide]: Mass=1269.74; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:19678698, ECO:0000269|PubMed:21047073};
CC -!- MASS SPECTROMETRY: [Nosiheptide]: Mass=1314.1467; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:19678698, ECO:0000269|PubMed:21047073};
CC -!- MISCELLANEOUS: The mature peptide is identical to multhiomycin from
CC S.antibioticus strain 8446CC1 (PMID 681244). {ECO:0000305}.
CC -!- MISCELLANEOUS: Used as an antibiotic growth promotant in poultry and
CC pig farming in parts of Asia. {ECO:0000303|PubMed:21836384}.
CC -!- SIMILARITY: Belongs to the thiocillin family. {ECO:0000255}.
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DR EMBL; FJ438820; ACR48342.1; -; Genomic_DNA.
DR PDB; 2ZJP; X-ray; 3.70 A; 5=38-50.
DR PDBsum; 2ZJP; -.
DR AlphaFoldDB; C6FX52; -.
DR SMR; C6FX52; -.
DR EvolutionaryTrace; C6FX52; -.
DR GO; GO:0070180; F:large ribosomal subunit rRNA binding; IDA:UniProtKB.
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:0045900; P:negative regulation of translational elongation; IDA:UniProtKB.
DR InterPro; IPR023895; Thiopep_bacteriocin_prcur.
DR TIGRFAMs; TIGR03892; thiopep_precurs; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Antibiotic; Antimicrobial; Hydroxylation;
KW Thioether bond.
FT CHAIN 1..50
FT /note="Nosiheptide precursor"
FT /id="PRO_0000414621"
FT PEPTIDE 38..49
FT /note="Nosiheptide"
FT /evidence="ECO:0000269|PubMed:19678698"
FT /id="PRO_0000414622"
FT MOD_RES 43
FT /note="4-hydroxyglutamate"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:19678698, ECO:0000269|PubMed:2584148,
FT ECO:0000269|PubMed:893891"
FT MOD_RES 49
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT MOD_RES 49
FT /note="Serine amide; atypical"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:21047073, ECO:0000269|PubMed:2584148,
FT ECO:0000269|PubMed:893891"
FT CROSSLNK 38..47
FT /note="3-hydroxypyridine-2,5-dicarboxylic acid (Ser-Ser)
FT (with C-46)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 38..46
FT /note="3-hydroxypyridine-2,5-dicarboxylic acid (Ser-Cys)
FT (with S-47)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 38..39
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 41..42
FT /note="Thiazole-4-carboxylic acid (Thr-Cys)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 43..45
FT /note="2-(cystein-S-ylcarbonyl)-3-methyl-4-(glutam-5-
FT yloxy)methylindole (Glu-Cys)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 43..44
FT /note="Thiazole-4-carboxylic acid (Glu-Cys)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 45..46
FT /note="Thiazole-4-carboxylic acid (Cys-Cys)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
FT CROSSLNK 47..48
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT /evidence="ECO:0000269|PubMed:18406324,
FT ECO:0000269|PubMed:2584148, ECO:0000269|PubMed:893891"
SQ SEQUENCE 50 AA; 5364 MW; 7ADF5924AF2C7D00 CRC64;
MDAAHLSDLD IDALEISEFL DESRLEDSEV VAKVMSASCT TCECCCSCSS
