ID THCL_PLARO Reviewed; 14 AA.
AC Q7M0J8;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 28-JUN-2023, entry version 40.
DE RecName: Full=Thiocillin GE2270;
DE AltName: Full=Antibiotic GE2270;
OS Planobispora rosea.
OC Bacteria; Actinomycetota; Actinomycetes; Streptosporangiales;
OC Streptosporangiaceae; Planobispora.
OX NCBI_TaxID=35762;
RN [1]
RP CHARACTERIZATION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 53773 / GE2270;
RX PubMed=1908853; DOI=10.7164/antibiotics.44.693;
RA Selva E., Beretta G., Montanini N., Saddler G.S., Gastaldo L., Ferrari P.,
RA Lorenzetti R., Landini P., Ripamonti F., Goldstein B.P., Berti M.,
RA Montanaro L., Denaro M.;
RT "Antibiotic GE2270 A: a novel inhibitor of bacterial protein synthesis. I.
RT Isolation and characterization.";
RL J. Antibiot. 44:693-701(1991).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 53773 / GE2270;
RX PubMed=7647369; DOI=10.1002/rcm.1290090817;
RA Colombo L., Stella S., Selva E.;
RT "Contribution of mass spectrometry to the structural confirmation of
RT components of the antibiotic GE2270 complex.";
RL Rapid Commun. Mass Spectrom. 9:717-722(1995).
RN [3]
RP MECHANISM OF ACTION ON EF-TU.
RX PubMed=16876786; DOI=10.1016/j.febslet.2006.07.039;
RA Parmeggiani A., Nissen P.;
RT "Elongation factor Tu-targeted antibiotics: four different structures, two
RT mechanisms of action.";
RL FEBS Lett. 580:4576-4581(2006).
RN [4]
RP STRUCTURE VERIFICATION BY CHEMICAL SYNTHESIS.
RX PubMed=17503407; DOI=10.1002/anie.200700684;
RA Muller H.M., Delgado O., Bach T.;
RT "Total synthesis of the thiazolyl peptide GE2270 A.";
RL Angew. Chem. Int. Ed. 46:4771-4774(2007).
RN [5]
RP STRUCTURE BY NMR, AMIDATION AT PRO-14, AND MASS SPECTROMETRY.
RC STRAIN=ATCC 53773 / GE2270;
RX PubMed=1880060; DOI=10.7164/antibiotics.44.702;
RA Kettenring J., Colombo L., Ferrari P., Tavecchia P., Nebuloni M., Vekey K.,
RA Gallo G.G., Selva E.;
RT "Antibiotic GE2270 A: a novel inhibitor of bacterial protein synthesis. II.
RT Structure elucidation.";
RL J. Antibiot. 44:702-715(1991).
RN [6]
RP SEQUENCE REVISION.
RC STRAIN=ATCC 53773 / GE2270;
RX PubMed=7844053; DOI=10.7164/antibiotics.47.1564;
RA Tavecchia P., Gentili P., Kurz M., Sottani C., Bonfichi R., Lociuro S.,
RA Selva E.;
RT "Revised structure of the antibiotic GE 2270A.";
RL J. Antibiot. 47:1564-1567(1994).
RN [7]
RP STRUCTURE BY NMR, AND METHYLATION AT ASN-3.
RC STRAIN=ATCC 53773 / GE2270;
RX PubMed=7592050; DOI=10.7164/antibiotics.48.1039;
RA Selva E., Ferrari P., Kurz M., Tavecchia P., Colombo L., Stella S.,
RA Restelli E., Goldstein B.P., Ripamonti F., Denaro M.;
RT "Components of the GE2270 complex produced by Planobispora rosea ATCC
RT 53773.";
RL J. Antibiot. 48:1039-1042(1995).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH EF-TU.
RX PubMed=10625477; DOI=10.1021/bi9913597;
RA Heffron S.E., Jurnak F.;
RT "Structure of an EF-Tu complex with a thiazolyl peptide antibiotic
RT determined at 2.35 A resolution: atomic basis for GE2270A inhibition of EF-
RT Tu.";
RL Biochemistry 39:37-45(2000).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH EF-TU.
RX PubMed=16734421; DOI=10.1021/bi0525122;
RA Parmeggiani A., Krab I.M., Okamura S., Nielsen R.C., Nyborg J., Nissen P.;
RT "Structural basis of the action of pulvomycin and GE2270 A on elongation
RT factor Tu.";
RL Biochemistry 45:6846-6857(2006).
CC -!- FUNCTION: Has bacteriocidal activity against Gram-positive bacteria and
CC a few Gram-negative bacteria. It is particularly active against
CC anaerobes. Inhibits bacterial protein biosynthesis by preventing the
CC formation of a stable complex between the elongation factor Tu (EF-Tu),
CC GTP and tRNA, hindering the activation of EF-Tu.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1908853}.
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 -!- PTM: The amidation of Pro-14 probably does not occur by the same
CC mechanism, oxidative cleavage of glycine, as in eukaryotes.
CC {ECO:0000305}.
CC -!- PTM: Several isomers, GE2270 A (GEA), B1, B2, C1, C2a, C2b, D1, D2, E
CC and T, are produced. The structural differences between them lie in the
CC extent of the modifications, methylation, methoxylation, and oxidation
CC of the thiazole and oxazole rings, and methylation of asparagine. They
CC are shown in PubMed:7592050. The modifications of form GE2270 A are
CC shown here.
CC -!- MASS SPECTROMETRY: Mass=1290.6; Mass_error=0.3; Method=FAB;
CC Evidence={ECO:0000269|PubMed:1880060};
CC -!- MISCELLANEOUS: Strain ATCC 23866 also produces this antibiotic.
CC -!- SIMILARITY: Belongs to the thiocillin family. {ECO:0000305}.
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DR PIR; A61210; A61210.
DR PDB; 1D8T; X-ray; 2.35 A; C/D=1-14.
DR PDB; 2C77; X-ray; 1.60 A; B=1-14.
DR PDB; 3U2Q; X-ray; 2.70 A; B=1-10.
DR PDB; 3U6B; X-ray; 2.12 A; C/D=1-10.
DR PDB; 3U6K; X-ray; 2.45 A; C/D=1-10.
DR PDBsum; 1D8T; -.
DR PDBsum; 2C77; -.
DR PDBsum; 3U2Q; -.
DR PDBsum; 3U6B; -.
DR PDBsum; 3U6K; -.
DR SMR; Q7M0J8; -.
DR iPTMnet; Q7M0J8; -.
DR EvolutionaryTrace; Q7M0J8; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Antibiotic; Antimicrobial; Bacteriocin;
KW Hydroxylation; Methylation; Secreted; Thioether bond.
FT PEPTIDE 1..14
FT /note="Thiocillin GE2270"
FT /id="PRO_0000363169"
FT MOD_RES 3
FT /note="N4-methylasparagine"
FT /evidence="ECO:0000305|PubMed:7592050"
FT MOD_RES 8
FT /note="3-hydroxyphenylalanine"
FT /evidence="ECO:0000250"
FT MOD_RES 14
FT /note="Proline amide"
FT /evidence="ECO:0000269|PubMed:1880060"
FT CROSSLNK 1..11
FT /note="Pyridine-2,5-dicarboxylic acid (Ser-Ser) (with C-
FT 10)"
FT CROSSLNK 1..10
FT /note="Pyridine-2,5-dicarboxylic acid (Ser-Cys) (with S-
FT 11)"
FT CROSSLNK 1..2
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT CROSSLNK 3..4
FT /note="5-methylthiazole-4-carboxylic acid (Asn-Cys)"
FT CROSSLNK 5..6
FT /note="5-(methoxymethyl)thiazole-4-carboxylic acid (Val-
FT Cys)"
FT CROSSLNK 8..9
FT /note="Thiazole-4-carboxylic acid (Phe-Cys)"
FT CROSSLNK 9..10
FT /note="Thiazole-4-carboxylic acid (Cys-Cys)"
FT CROSSLNK 11..12
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT CROSSLNK 12..13
FT /note="Oxazoline-4-carboxylic acid (Cys-Ser)"
SQ SEQUENCE 14 AA; 1413 MW; 3EB862761A7766C8 CRC64;
SCNCVCGFCC SCSP
//
