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Literature summary extracted from

  • Osterman, I.A.; Khabibullina, N.F.; Komarova, E.S.; Kasatsky, P.; Kartsev, V.G.; Bogdanov, A.A.; Dontsova, O.A.; Konevega, A.L.; Sergiev, P.V.; Polikanov, Y.S.
    Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state (2017), Nucleic Acids Res., 45, 7507-7514 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.3.2.12 Thermus thermophilus 70S ribosomes complexed with mRNA and P-site (fMet-tRNAifMet) and A-site (Phe-tRNAPhe) substrates, co-crystallization of inhibitor madumycin II, sitting drop vapor diffusion method, 70S ribosome complexes are formed in buffer containing 5 mM HEPES-KOH, pH 7.6, 50 mM KCl, 10 mM NH4Cl, and 10 mM Mg(CH3COO)2, and then crystallized in buffer containing 100 mM Tris-HCl, pH 7.6, 2.9% w/v PEG 20000, 7-12% v/v MPD, 100-200 mM arginine, 0.5 mM 2-mercaptoethanol, 19°C, X-ray diffraction structure determination and analysis at 2.8 A resolution, molecular replacement, structure modeling Thermus thermophilus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.2.12 madumycin II i.e. MADU, an alanine-containing streptogramin A antibiotic, inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. Drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506-G2583 wobble pair that is attributed to a catalytically inactive state of the PTC. At 0.005 mM concentration, MADU reduces the efficiency of protein synthesis by over 100fold Escherichia coli
2.3.2.12 madumycin II i.e. MADU, an alanine-containing streptogramin A antibiotic, inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. Drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506-G2583 wobble pair that is attributed to a catalytically inactive state of the PTC. Structures of inhibitor madumycin II in complex with the 70S ribosome and A- and P-tRNAs, overview Thermus thermophilus
2.3.2.12 additional information streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome Escherichia coli
2.3.2.12 additional information streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In ribosome complex with mRNA and tRNAs, the binding site of madumycin II is very similar to the binding sites of virginiamycin M, dalfopristin, or flopristin (all proline-containing type A streptogramin antibiotics) Thermus thermophilus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.2.12 ribosome 70S ribosome Thermus thermophilus 5840
-
2.3.2.12 ribosome 70S ribosome Escherichia coli 5840
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.2.12 Mg2+ required Thermus thermophilus
2.3.2.12 Mg2+ required Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.12 peptidyl-tRNA1 + aminoacyl-tRNA2 Thermus thermophilus
-
 tRNA1 + peptidyl(aminoacyl-tRNA2)
-
 ?
2.3.2.12 peptidyl-tRNA1 + aminoacyl-tRNA2 Escherichia coli
-
 tRNA1 + peptidyl(aminoacyl-tRNA2)
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.12 Escherichia coli
-
-
-
2.3.2.12 Thermus thermophilus
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.12 fMet-Phe-tRNAPhe + puromycin
-
 Thermus thermophilus tRNAPhe + fMet-Phe-puromycin
-
 ?
2.3.2.12 fMet-Phe-tRNAPhe + puromycin
-
 Escherichia coli tRNAPhe + fMet-Phe-puromycin
-
 ?
2.3.2.12 fMet-tRNAfMet + Phe-tRNAPhe
-
 Thermus thermophilus tRNAfMet + fMet(Phe-tRNA2)
-
 ?
2.3.2.12 fMet-tRNAfMet + Phe-tRNAPhe
-
 Escherichia coli tRNAfMet + fMet(Phe-tRNA2)
-
 ?
2.3.2.12 fMet-Val-tRNAVal + Phe-tRNAPhe
-
 Thermus thermophilus tRNAVal + fMet-Val(Phe-tRNA2)
-
 ?
2.3.2.12 fMet-Val-tRNAVal + Phe-tRNAPhe
-
 Escherichia coli tRNAVal + fMet-Val(Phe-tRNA2)
-
 ?
2.3.2.12 additional information the peptidyl transferase reaction is monitored by fMet-Phe dipeptide, fMet-Phe-puromycin, and fMet-Val-Phe tripeptide formation assays Thermus thermophilus ?
-
-
2.3.2.12 additional information the peptidyl transferase reaction is monitored by fMet-Phe dipeptide, fMet-Phe-puromycin, and fMet-Val-Phe tripeptide formation assays Escherichia coli ?
-
-
2.3.2.12 peptidyl-tRNA1 + aminoacyl-tRNA2
-
 Thermus thermophilus tRNA1 + peptidyl(aminoacyl-tRNA2)
-
 ?
2.3.2.12 peptidyl-tRNA1 + aminoacyl-tRNA2
-
 Escherichia coli tRNA1 + peptidyl(aminoacyl-tRNA2)
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.2.12 peptidyl transferase center
-
 Thermus thermophilus
2.3.2.12 peptidyl transferase center
-
 Escherichia coli
2.3.2.12 PTC
-
 Thermus thermophilus
2.3.2.12 PTC
-
 Escherichia coli

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.2.12 37
-
 assay at Thermus thermophilus
2.3.2.12 37
-
 assay at Escherichia coli

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.2.12 7.5
-
 assay at Thermus thermophilus
2.3.2.12 7.5
-
 assay at Escherichia coli

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.2.12 0.0003
-
 pH 7.5, 37°C Escherichia coli madumycin II

General Information

EC Number General Information Comment Organism
2.3.2.12 additional information the enzyme is part of the peptidyl transferase center (PTC) Thermus thermophilus
2.3.2.12 additional information the enzyme is part of the peptidyl transferase center (PTC) Escherichia coli