THCL_STRSQ
ID THCL_STRSQ Reviewed; 57 AA.
AC P0C8P9; G1ECL0;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 2.
DT 25-MAY-2022, entry version 19.
DE RecName: Full=Thiocillin GE37468;
DE AltName: Full=Antibiotic GE37468;
DE Flags: Precursor;
GN Name=getA;
OS Streptomyces sp.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1931;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, MASS SPECTROMETRY,
RP METHYLHYDROXYLATION AT ILE-50, AND MUTAGENESIS OF ILE-50.
RC STRAIN=ATCC 55365;
RX PubMed=21788474; DOI=10.1073/pnas.1110435108;
RA Young T.S., Walsh C.T.;
RT "Identification of the thiazolyl peptide GE37468 gene cluster from
RT Streptomyces ATCC 55365 and heterologous expression in Streptomyces
RT lividans.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:13053-13058(2011).
RN [2]
RP CHARACTERIZATION, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=ATCC 55365;
RX PubMed=7592021; DOI=10.7164/antibiotics.48.780;
RA Stella S., Montanini N., Le Monnier F., Ferrari P., Colombo L., Landini P.,
RA Ciciliato I., Goldstein B.P., Selva E., Denaro M.;
RT "Antibiotic GE37468 A: a new inhibitor of bacterial protein synthesis. I.
RT Isolation and characterization.";
RL J. Antibiot. 48:780-786(1995).
RN [3]
RP STRUCTURE BY NMR, MASS SPECTROMETRY, AND DEHYDRATION AT SER-55 AND SER-56.
RC STRAIN=ATCC 55365;
RX PubMed=8557573; DOI=10.7164/antibiotics.48.1304;
RA Ferrari P., Colombo L., Stella S., Selva E., Zerilli L.F.;
RT "Antibiotic GE37468 A: a novel inhibitor of bacterial protein synthesis.
RT II. Structure elucidation.";
RL J. Antibiot. 48:1304-1311(1995).
CC -!- FUNCTION: Has bacteriocidal activity against both aerobic and anaerobic
CC Gram-positive bacteria. Inhibits growth of B.subtilis (MIC=0.047 ug/ml)
CC and methicillin-resistant S.aureus (MRSA) (MIC=0.047 ug/ml). Has poor
CC activity against Gram-negative bacteria, with the exception of
CC B.fragilis. Inhibits bacterial protein biosynthesis by acting on
CC elongation factor Tu (EF-Tu). Full antibiotic activity depends on the
CC presence of the modified residue Ile-50. {ECO:0000269|PubMed:21788474}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7592021}.
CC -!- PTM: Maturation of thiazole and oxazole containing antibiotics involves
CC the enzymatic condensation of a Cys, Ser or Thr with the alpha-carbonyl
CC of the preceding amino acid to form a thioether or ether bond, then
CC dehydration to form a double bond with the alpha-amino nitrogen.
CC Thiazoline or oxazoline ring are dehydrogenated to form thiazole or
CC oxazole rings.
CC -!- PTM: Maturation of pyridinyl containing antibiotics involves the cross-
CC linking of a Ser and a Cys-Ser pair usually separated by 7 or 8
CC residues along the peptide chain. The Ser residues are dehydrated to
CC didehydroalanines, then bonded between their beta carbons. The alpha
CC carbonyl of the Cys condenses with alpha carbon of the first Ser to
CC form a pyridinyl ring. The ring may be multiply dehydrogenated to form
CC a pyridine ring with loss of the amino nitrogen of the first Ser.
CC -!- MASS SPECTROMETRY: Mass=1309.48; Method=FAB;
CC Evidence={ECO:0000269|PubMed:8557573};
CC -!- MASS SPECTROMETRY: Mass=1308.247; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:21788474};
CC -!- SIMILARITY: Belongs to the thiocillin family. {ECO:0000305}.
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DR EMBL; JN052143; AEM00614.1; -; Genomic_DNA.
DR AlphaFoldDB; P0C8P9; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030371; F:translation repressor activity; 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:0017148; P:negative regulation of translation; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Bacteriocin; Hydroxylation; Methylation;
KW Secreted; Thioether bond.
FT PROPEP 1..42
FT /note="Removed in mature form"
FT /id="PRO_0000414924"
FT PEPTIDE 43..56
FT /note="Thiocillin GE37468"
FT /id="PRO_0000363171"
FT PROPEP 57
FT /note="Removed in mature form"
FT /id="PRO_0000414925"
FT MOD_RES 50
FT /note="5-hydroxy-3-methylproline (Ile)"
FT /evidence="ECO:0000269|PubMed:21788474"
FT MOD_RES 55
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000269|PubMed:8557573"
FT MOD_RES 56
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000269|PubMed:8557573"
FT CROSSLNK 43..53
FT /note="Pyridine-2,5-dicarboxylic acid (Ser-Ser) (with C-
FT 52)"
FT CROSSLNK 43..52
FT /note="Pyridine-2,5-dicarboxylic acid (Ser-Cys) (with S-
FT 53)"
FT CROSSLNK 43..44
FT /note="5-methyloxazole-4-carboxylic acid (Ser-Thr)"
FT CROSSLNK 45..46
FT /note="Thiazole-4-carboxylic acid (Asn-Cys)"
FT CROSSLNK 47..48
FT /note="Thiazoline-4-carboxylic acid (Phe-Cys)"
FT CROSSLNK 50..51
FT /note="Thiazole-4-carboxylic acid (Ile-Cys)"
FT CROSSLNK 51..52
FT /note="Thiazole-4-carboxylic acid (Cys-Cys)"
FT CROSSLNK 53..54
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT MUTAGEN 50
FT /note="I->A: Two-fold decrease in antibiotic activity."
FT /evidence="ECO:0000269|PubMed:21788474"
SQ SEQUENCE 57 AA; 6058 MW; 1B62126BDED6078B CRC64;
MGNNEEYFID VNDLSIDVFD VVEQGGAVTA LTADHGMPEV GASTNCFCYI CCSCSSN
