BIRD-PRD_000225: GE2270a

Basic information

• Entry: Database: Biologically Interesting Molecule Reference Dictionary (BIRD) / ID: PRD_000225
• Status: Status: REF ONLY
• Name: GE2270a

BIRD information

• Type: Thiopeptide / Antibiotic

Details

• GEA2270A is a member of a sulphur-rich heterocyclic peptides class. All members share a macrocylic core, consisting of a nitrogen containing, six-membered ring central to dehydroamino acids and a subset of five member ring structures including thiazoles, thiazolines and oxazoles. Post translational maturation of thiazole and oxazole containing antibiotics involves the enzymic condensation of a Cys or Ser with the alpha- carbonyl of the preceding amino acid to form a thioether or ether bond, then dehydration to form a double bond with the alpha-amino nitrogen. Thiazoline or oxazoline ring are dehydrogenated to form thiazole or oxazole rings. In addition cross-linking of a Ser and a Cys-Ser pair usually separated by 7 or 8 residues along the peptide chain produce a pyridinyl ring. The Ser residues are dehydrated to didehydroalanines, then bonded between their beta carbons. The alpha carbonyl of the Cys condenses with alpha carbon of the first Ser to form a pyridinyl ring. The ring may be mutiply dehydrogenated to form a pyridine ring with loss of the amino nitrogen of the first Ser. Several isomers are produced. The structural differences between them lie in the extent of the modifications, methylation, methoxylation, and oxidation of the thiazole and oxazole rings, and methylation of asparagine. The amidation of Pro-14 probably does not occur by the same mechanism, oxidative cleavage of glycine, as in eukaryotes.
• GEA2270A IS A THIOPEPTIDE CONSISTING OF ONE PYRIDINE, ONE OXAZOLE AND FIVE THIAZOLE RINGS. THE OBSERVED C-TERMINAL AMINO GROUP NH2(15) IS LIKELY TO BE A POST-TRANSLATIONAL DECARBOXYLATED REMNANT OF A SER C-TERMINAL RESIDUE.

• Downloads: Molecular definition / Chemical definition / Family definition

Synonyms

• 1-{[2-(2-{35-[hydroxy(phenyl)methyl]-28-(methoxymethyl)-21-methyl-18-[(methylcarbamoyl)methyl]-16,23,30,33-tetraoxo-25-(propan-2-yl)-3,13,20,27,37-pentathia-7,17,24,31,34,39,40,41,42,43-decaazaheptacyclo[34.2.1.1^{2,5}.1^{12,15}.1^{19,22}.1^{26,29}.0^{6,11}]tritetraconta-1(38),2(43),4,6(11),7,9,12(42),14,19(41),21,26(40),28,36(39)-tridecaen-8-yl}-1,3-thiazol-4-yl)-4,5-dihydro-1,3-oxazol-4-yl]carbonyl}pyrrolidine-2-carboxamide (DrugBank)
• 2-Hydroxy-3,9,10-trimethoxy-5,6-dihydro-isochino[3,2-a]isochinolinylium(Jodid) (Beilstein)
• 2-Hydroxy-3,9,10-trimethoxy-5,6-dihydro-isoquino[3,2-a]isoquinolinylium(io (Beilstein)
• 2-hydroxy-3,9,10-trimethoxy-5,6-dihydro-isoquino[3,2-a]isoquinolinylium(iodide) (Beilstein)
• Berbinium, 7,8,13,13a-tetradehydro-2-hydroxy-3,9,10-trimethoxy-, iodide (8CI) (SciFinder)
• Columbamine, iodide (7CI) (SciFinder)
• Dibenzo[a,g]quinolizinium, 5,6-dihydro-2-hydroxy-3,9,10-trimethoxy-, iodide (9CI) (SciFinder)
• GE2270A (PubChem)
• THIOCILIN GE2270 (PDB)
• Thiocillin GE2270 (UniProt)
• dehydrocorydalmine (Beilstein)

Annotation

• Function: Has bacteriocidal activity against Gram-positive bacteria and a few Gram-negative bacteria. It is particularly active against anaerobes. Inhibits bacterial protein biosynthesis by preventing the formation of a stable complex between the elongation factor Tu (EF-Tu), GTP and tRNA, hindering the activation of EF-Tu. / Info source: UniProt

Source

• Planobispora rosea (bacteria), NADB: 440127
• Planobispora rosea (bacteria), UniProt: Q7M0J8

External info

• Beilstein: 3831132
• ChemBank: 832290
• ChemDB: 3966755
• DrugBank: DB02975
• ChemSpider: 17290366
• PubChem: 16133784
• CAS: 2007-07-0
• [KEGG_Compound_ID] KEGG: C12068
• [MESH_Unique_ID] MESH: C068122

Family

Thiopeptides

Nosiheptide / THIOSTREPTON / GE2270a / THIOPEPTIDE THIOSTREPTON REDUCED AT N-CA BOND OF RESIDUE 14 / THIOPEPTIDE THIOSTREPTON WITH EPIMER FORM OF RESIDUE 9 / THIOPEPTIDE THIOSTREPTON OXIDIZED AT CA-CB BOND OF RESIDUE 9 / Thiocillin GE2270 analogue NVP-LFF571 / Thiocillin GE2270 analogue NVP-LDK733 / Thiocillin GE2270 analogue NVP-LDI028 / thiomuracin A derivative

Related structures

• Thiostrepton / CCDC: TSTREP / Reference
• Nosiheptide chloroform solvate / CCDC: NOSHEP10 / Reference

Chemical information

Composition

Formula: C₅₆H₅₈N₁₅O₁₀S₆ / Formula weight: 1293.544

• Others: Type: peptide-like

History

• External links: UniChem / ChemSpider / Wikipedia search / Google search

Details

SMILES

• CACTVS 3.370: CNC(=O)C[CH]1NC(=O)c2csc(n2)[CH]3CC[C](=[N]=[C]3c4csc(n4)c5csc(n5)[CH](NC(=O)CNC(=O)c6nc(sc6COC)[CH](NC(=O)c7nc1sc7C)C(C)C)[CH](O)c8ccccc8)c9scc(n9)C%10=N[CH](CO%10)C(=O)N%11CCC[CH]%11C(N)=O
• OpenEye OEToolkits 1.7.6: Cc1c2nc(s1)C(NC(=O)c3csc(n3)C4CCC(=[N]=C4c5csc(n5)-c6csc(n6)C(NC(=O)CNC(=O)c7c(sc(n7)C(NC2=O)C(C)C)COC)C(c8ccccc8)O)c9nc(cs9)C1=NC(CO1)C(=O)N1CCCC1C(=O)N)CC(=O)NC

SMILES CANONICAL

• CACTVS 3.370: CNC(=O)C[C@@H]1NC(=O)c2csc(n2)[C@H]3CC[C](=[N]=[C]3c4csc(n4)c5csc(n5)[C@@H](NC(=O)CNC(=O)c6nc(sc6COC)[C@@H](NC(=O)c7nc1sc7C)C(C)C)[C@H](O)c8ccccc8)c9scc(n9)C%10=N[C@@H](CO%10)C(=O)N%11CCC[C@H]%11C(N)=O
• OpenEye OEToolkits 1.7.6: Cc1c2nc(s1)[C@@H](NC(=O)c3csc(n3)[C@@H]4CCC(=[N]=C4c5csc(n5)-c6csc(n6)[C@@H](NC(=O)CNC(=O)c7c(sc(n7)[C@@H](NC2=O)C(C)C)COC)[C@@H](c8ccccc8)O)c9nc(cs9)C1=N[C@@H](CO1)C(=O)N1CCC[C@H]1C(=O)N)CC(=O)NC

InChI

• InChI 1.03: InChI=1S/C56H58N15O10S6/c1-24(2)39-55-70-42(36(87-55)19-80-5)47(77)59-17-38(73)67-43(44(74)26-10-7-6-8-11-26)54-66-34(23-85-54)52-63-31(20-83-52)41-27(50-64-32(21-82-50)46(76)61-29(16-37(72)58-4)53-69-40(25(3)86-53)48(78)68-39)13-14-28(60-41)51-65-33(22-84-51)49-62-30(18-81-49)56(79)71-15-9-12-35(71)45(57)75/h6-8,10-11,20-24,27,29-30,35,39,43-44,74H,9,12-19H2,1-5H3,(H2,57,75)(H,58,72)(H,59,77)(H,61,76)(H,67,73)(H,68,78)

InChIKey

• InChI 1.03: UMPNWRLEAJXFKB-UHFFFAOYSA-N

PDB entries

Showing all 2 items

PDB-1d8t:
CRYSTAL STRUCTURE OF ELONGATION FACTOR, TU (EF-TU-MGGDP) COMPLEXED WITH GE2270A, A THIAZOLYL PEPTIDE ANTIBIOTIC

PDB-2c77:
EF-Tu complexed with a GTP analog and the antibiotic GE2270 A